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CONTEMPORARY DIAGNOSTIC AND TREATMENT OF PATIENTS WITH STROKE by: “European Stroke Initiative Recommendations for Stroke Management”


CONTEMPORARY DIAGNOSTIC AND TREATMENT OF PATIENTS WITH STROKE by: “European Stroke Initiative Recommendations for Stroke Management”

Academician Dr. Zan Mitrev Dr. Tanja Angjusheva, Prof. Dr. Liljana Ilievska and Prof. Dr. Dijana Nikodijević

Skopje, 2010


Contents INTRODUCTION ORGANIZATION OF STROKE CARE: EDUCATION, REFERRAL, STROKE UNITS AND REHABILITATION Education ....................................................................................................................................................................... .6 Referral ........................................................................................................................................................................... 7 Stroke units..................................................................................................................................................................... 8 Emergency management..............................................................................................................................................10 Quality management and quality control process ...................................................................................................11 Rehabilitation................................................................................................................................................................11 PREVENTION PRIMARY PREVENTION...........................................................................................................................................12 Antithrombotic therapy ...........................................................................................................15 Carotid surgery and endovascular treatment of asymptomatic carotid stenosis..................................................16 SECONDARY PREVENTION.....................................................................................................................................17 Antithrombotic therapy ..............................................................................................................................................17 Anticoagulation............................................................................................................................................................18 Antihypertensive therapy ...........................................................................................................................................18 Cholesterol-lowering therapy ....................................................................................................................................18 Hormone therapy..........................................................................................................................................................18 Smoking ........................................................................................................................................................................18 Carotid Endarterectomy (CEA) . ................................................................................................................................18 Carotid Angioplasty and Stenting .............................................................................................................................19 Acute Stroke Management..........................................................................................................................................20 Pulmonary function or airway protection.................................................................................................................20 Managing Blood Pressure ...........................................................................................................................................20 Glucose Metabolism pathway.....................................................................................................................................23 SPECIFIC TREATMENT Prevention and treatment of complications..............................................................................................................25 Brain edema and elevated ICP....................................................................................................................................25 Medical therapy ...........................................................................................................................................................25 REFERENCES SUPLEMENT


INTRODUCTION “European Stroke Initiative Recommendations for Stroke Management” are first published in January 2000. The first publication was well accepted and it was accompanied by a longer suplement about cerebrovascular deseases. Three years later, “European Stroke Initiative (EUSI) Executive Committee” felt that there were already enough new data to justify the full revision of existing recommendations. Levels of evidence in this paper are defined according to the same criteria as the previous recommendations. They correspond to those published by the “European Federation of Neurologic Society.”

Table 1. Definitions of levels of evidence for these recommendations. Level 1 Sources

The highest level of evidence a. Primary “endpoint” of RTC with an adequate number of samples b. Meta analysis of RTC that are excellent by quality

Level 2 Sources

Intermeadiall level of evidence a. Small randomized studies b. Predefined secular “endpoints” of the big RTC

Level 3 Sources

Evidence for low-level a. Series of prospective cases with concurrent or with a history of controll b. Post hoc analysis of the big RTC

Level 4 Sources

Level of evidence remains undefined a. Small uncontrolled series of cases b. General agreement despite the lack of evidence

ORGANIZATION OF STROKE CARE:EDUCATION, REFERRAL, STROKE UNITS AND REHABILITATION Acute stroke is one of the leading factors of worldwide morbidity and mortality. Strokes are ranged as the second or third most common causes of death in developed countries, after cardiovascular diseases. In Europe, crude mortality rate ranges from 63.4/100, 000 (men, Svitzerland 1992) to 273.4/100, 000 (females, Russia 2001). These various differences in mortality between Eastern and Western Europe are associated with differences in expression of the risk - factors (high hipertension and other risks in the Eastern countries compared to Western), thus resulting in higher stroke rates in Eastern Europe. Also, regional variations are reported in Western countries. Stroke, as the most important factor for mortality and long-term disability in Europe, imposes a big economic burden. The mean value of the costs for the first heart attack that leads to death, was calculated for some Europian countries, for example, in Sweden it is about 79.000 euros. Over the past decades, acute stroke is incresingly recognized as a medical emergency case. Acute, postacute rehabilitation care for patients with stroke in a special units and revascular therapeutics are proven as successful in the acute ischaemic stroke. The establishment of a network consists of acute stroke units, prolonged postacute care and rehabilitation, and also aftercare in the society, as a standard treatment in many European countries. Care systems include national concepts for stroke care units focusing on acute care, as in Austria and Germany, and systems of separate stroke units focusing on comprehensive care, including rehabilitation, as in the UK or in Scandinavia.


Over the last few years, few publications of European guidance and documents for concenzus are published and they include reports from “Pan European Ad Hoc Consensus Group, The Task Force on Acute Neurological Stroke Care of the European Federation of Neurological Societies, and “The EUSI”. Among northamerican guidlance and recommendations for treatment published by “The American Academy of Neurology” are those for acute treatment, carotid surgery, transient ischemic attack menagement and primary prevention of stroke. Earlier recommendations are published by WHO.

Education Family dsoctor also need to be trained to recognize the symptoms and signs of acute stroke and for the need for immediate transport to adequately equipped unit. Medical staff should be trained to recognize presentations of acute ischemic stroke and to deal with early complications after stroke. Training should include an opportunity for implementation of medical examination that focuses on the level of consciousness, the presence of focal weakness, presence of attacks and the recognition of aphasia and other major cognitive disabilities. The concept of “Time is brain” should be understood by all involved in the “stroke chain of survival”. It should not be allowed waste of time when the patient presents in the hospital and there should be written standards for the hospital delays in hospitals receiving patients with stroke. Although these paths are


not effective itself, they could be considered as effective in the prevention of delays in hospitals.

Referral Stroke is a medical and sometimes also surgical emergency case. Successful care for victims of acute stroke begins with the recognition of both groups, public and a health professional, that stroke is an emergency case, such as acute myocardial infarct (AMI) and trauma. Most patients with stroke do not receive adequate therapy because they do not present at the hospitals on time. Successful care for victims of acute stroke, as an emergency case, depends on 4 steps in the chain: 1) rapid recognition of symptoms and response to warning signs of stroke, 2) the immediate use of an emergency medical service system (EMS), 3) priority transport by reporting the hospital that receives the patient, 4) prompt and adequate diagnosis and treatment in the hospital. When once appeared suspicion that the symptoms are result of stroke, patients or their proxies should make contact with EMS. Ambulance transport reduces late arrival in hospital after innicial stroke (level 3). Transport with helicopter has increased role in transfer of patients with stroke between hospitals and should be activated earlier. EMS should have an electronic validated algoritm of questions to diagnose stroke during a telephone interview with the patient / proxy. The patients during the first 3 hours of the onset of stroke should be given priority in evaluation / transportation by EMS. EMS ambulance dispatchers should be able to recognize symptoms and signs of stroke and to identify and implement appropriate help for patients who need urgent care due to impared consciousness, seizures, vomiting, hemodynamic instability or other early complications or comorbidity on stroke. Tools that are often used in prehospital a stroke rates assements are either “Cincinnati Prehospital Stroke Scale” or “Los Angeles Prehospital Stroke Scale” test, and the tool used for estimation of the acute condition is “NIH Stroke Scale” test. (Tests can be viewed in the appendix). The initial evaluation of patients with stroke can be

done by the doctors in the Emegerncy Center. Specifically, doctors from the Emegerncy Center can properly establish the diagnosis of stroke in about 90% of cases. Recommendations 1

1. Patients with first stroke should be treated in the stroke units (level 1). Therefore, suspected victims of stroke should be transported without delay to the nearest medical center with available stroke unit or to the hospital that provides organized acute stroke care if the unit of stroke is not available. 2. Once as symptoms of stroke are established, patients or their proxies should present in EMS or in a similar system (level 3). 3. Patients with subaroid haemorrhage should be addressed urgently in the center with conditions for neurosurgical treatment, neuroradiological interventions and neurointensive care (level 1).


Stroke units

Care of patients with stroke should be performed in stroke units. Stroke units consists of hospital unit or part of the hospital unit where exclusively or almost exclusively are caring stroke patients. Analysis carried out across Europe show that there are different types of stroke units. Most of these units provide coordinated multidisciplinary approach to stroke treatment and care. The basic disciplines of the multidisciplinary team are: medical treatment, care, physiotherapy, occupational therapy, speech and language therapy and social work. Stroke units are described in several categories: 1. Acute stroke unit where acute patients who continue with the treatment several days, but usually less than 1 week, are admitted. 2. Comprehensive stroke unit where acute patients

who continue with the treatment and rehabilitation up to several weeks if necessary are admitted. 3. Stroke rehabilitation unit where patients are admitted after 1 or 2 weeks and where they continue with the treatment and rehabilitation even up to several months if necessary, and 4. A mobile stroke team, who offers care and treatment of stroke patients in different units. These teams are established mainly in hospitals where there is no stroke unit. From all of these, only comprehensive treatment unit and the rehabilitation unit have proven efficiency in terms of reduced mortality and disability.


Table 2. Basis for stroke management

Minimum requirements for Centers managing stroke patients 1. 24 - hour availability of CT scan 2. Establishment of guidelines for treatment of stroke and surgical procedures 3. Close cooperation with neurologists, internists and rehabilitation experts 4. Specially trained nursing staff 5. Early multidisciplinary rehabilitation including speech and language therapy, occupational therapy and physical therapy 6. Establishing a network of rehabilitation facilities that would provide a continuous process of rehabilitation care 7. Neurological examinations within 24 hours (extracranial blood vessels, “color-coded duplex� sonography) 8. ECG 9. Laboratory examinations (including coagulative parameters) 10. Monitoring of blood pressure, ECG, oxygen saturation, blood glucose, body temperature Additional preparations recommended 1. MRI / MRA 2. Diffusional and perfusional MR 3. CTA 4. ECG (TEE) 5. Cerebral angiography 6. Transcranial Doppler sonography 7. Specialized neurological, neurosurgical and vascular surgical consultations Recommendations 2

1. Patients with stroke should be treated in the stroke units (level 1) 2. Stroke units should provide coordinated multidisciplinary care that would offer medical, nursing and therapeutic staff specialized in care of patients with stroke


Emergency management The time interval for the treatment of patients with acute stroke is narrowing. Therefore, emergency acute stroke management requires parallel processes at different levels in managing the patients. Patients with acute stroke, even those with milder symptoms should be recognized as critically ill medical patients. The patient should be transported in an emergency unit and physician who will examine the patient should treat the patient with stroke with a priority, as with disabling and life-threating desease. Only a small part of patients with stroke immediately show life-threatening condition, but many of them have severe abnormalities in basic physiological functions. Symptoms and signs that can predict further complications such as heart attack or bleeding, repeated stroke and medical conditions such as hypertensive crises, existing MI, aspiration pneumonia and renal failure must be early recognized. Also, there is a need for early definition of stroke subtypes based on

physical and neurological evaluation, and interpretation of capabilities based on the results of CT and magnetic resonance imaging (MRI) wich are essential for predicting high risk of early recurrence. The initial examination includes observation of respiratory and pulmonary functions, associated heart disease, monitoring blood pressure and heart rhythm and determination of oxygen saturation using infrared pulse oximetry, if available. At the same time, samples of blood are taken for clinical chemistry, coagulation and hematology studies and the venous line is set. Standard electrolyte solutions are given, until clinical chemical results become available. After emergency care, neurologist should implement targeted neurological examinations. Examinations are accompanied, if possible, with careful medical history focusing on risk - factors for atherosclerosis and heart deseases, and in young patients history of drug abuse use of oral contraceptives, trauma or migraine, may be an important indicator.


Table 3. Urgent diagnostic tests in patients with acute stroke

1. CT 2. ECG and chest X-ray 3. Clinical chemistry • Complete blood and platelets count, prothrombin time, INR, PTT • Serum erythrocytes, blood glucose • CRP, sedimentation • Gas analysis of arterial blood, if there is suspected hipoxia • Hepatic and renal chemical analysis 4. Pulse oximetry 5. Lumbar puncture (only if CT is negative, CT and subarahnoid haemorrhage is clinically suspected) 6. Duplex and Transcranial Doopler Ultrasound 7. EEG 8. MRI and MRA / CTA 9. Difusion MR and perfusion MR 10. ECG (TEE and TTE)

Quality management and quality control of the process Table 4. Recommendations for quality control of the timeframe of acute stroke treatment

Time interval

Time goal

Access to neurological expert

15 мин.

Access to CT imaging - completing

25 мин.

Access to CT imaging - interpretation

45 мин.

Access to treatment

60 мин.

Admission to monitor bed

3 ч.

From admission to doctor

10 мин.

Rehabilitation 40% of stroke patients need active rehabilitation services. Rehabilitation of stroke victims should begin as soon as possible after the patients become clinically stable. Intensity of rehabilitational program depends on patient’s status and the level of disability. Once the patient is stable, he/she should be carefully evaluated for the levels of disability. Degree and distribution of motor weakness, associated sensory and proprioseptive deficits should be carefully registered. The assessment should include evaluation of intellectual impairment, especially of specific cognitive deficits such as aphasia, agnosia, disorders of memory and attention and wide range of emotional instability and motivational disorders.When the patient is transferred to Rehabilitation Hospital, it is of great importance that all members of the stroke team should give all documents


of patient`s progress to the stroke team in Rehabilitation hospital. After the institutional rehabilitation, rehabilitation program can be transferred in Outpatient Rehabilitation Clinics. This provides a spontaneous transfer of the patient to the next rehabilitationalstep back to normal. The lenght of the rehabilitation period in the acute phase depends on the severity of stroke and local access to rehabilitation services for stroke. Under normal conditions, rehabilitation after acute phase of ischemic stroke should not be longer than 6 to 12 weeks and rarely more than 24 weeks. Recommendations 3.

1. Every patient should have access to the evaluation of rehabilitation. 2. In patients with obvious indications for rehabilitation, treatment should be initiated immediately after the stroke (level 1). Unabled patients should have access to structural elements of stroke care including and institutional care. 3. Rehabilitation should provide a multidisciplinary team for good stroke unit care (level 1). 4. Intensity and duration of rehabilitation should be optimal for every patient and should apply new methods of rehabilitation (e.g., recurrent training and use of force), ideally in additon to the basic methods. 5. Patients with chronic symptomatic stroke should be supported in their social environment. This includes access to family doctor, and evaluation of outpatient rehabilitation services, secondary prevention and support in psychosocial function. (level 2).

PREVENTION PRIMARY PREVENTION Primary prevention aims to reduce the risk of stroke in asimtomatic people. Recommendations about patients with TIA, here are regarded as secondary prevention. The relative reduction risk (RRR), absolute risk reduction (ARR) and NNT to avoid one major vascular event per year are presented in the following tables. Table 5. RRR, ARR, NNT to avoid one stroke per year in patients who have a surgery due to ICA stenosis

Disease

NNT to avoid 1 stroke / per year

RRR%

ARR / % per year

Asymptomatic (60-99%)

53

1.2

Symptomatic (70-99%)

65

3.8

27

Symptomatic (50-69%)

29

1.3

75

Symptomatic (> 50%)

No benefits

No benefits

No benefits

85


Table 6. RRR, ARR and NNT to avoid 1 major vascular event per year in patients with antithrombotic therapy

Disease

Treatment

RRR%

ARR/ % per year

NNT to avoid 1 major vascular event / per year

Without cardiac embolism

ASA/ placebo

13

1.0

100

15

0.9

111

Ischemic stroke or TIA

ASA+ DIP/ aspirin ASA+ DIP/ placebo Copidogrel/ ASA

19

1.2

13

0.6

53 1 66

AF (primary prevention)

Warfarin/ placebo ASA/placebo

62

2.7

37

22

1.7

67

AF (secondary prevention)

Warfarin/ placebo ASA/placebo

67

8

13

21

2.5

40

Table 7. RRR, ARR, NNT to avoid 1 major vascular event per year in patients with modified risk factors. .

Clinical condition

Treatment

RRR %

ARR %

NNT to avoid 1 stroke event / per year

antihypertensives

42

0.2

94

Post stroke / TIA with increased pressure

antihypertensives

31

2.2

45

Post stroke / TIA with normal pressure

antihypertensives

28

4

42

статини престанок на пушење

24 33

1.7 2.3

59 43

General population with increased pressure

Post stroke / TIA


Recommendations 4.

1. Measurement of blood pressure is a fundamental part of the regular health care during a visit. Blood pressure must be reduced to normal level (<140 / <90 mm Hg or <130 / <80 mm Hg in diabetics) by means of modifications for activities in daily living. Most hypertensive patients also will require pharmacological treatment to achieve a normal pressure level (level 1). 2. Although strict control of blood glucose levels in diabetes melitus is not proven to be associated with lower risk of stroke, patients should be encouraged because of benefits on behalf of other complicationsof diabetes (level 3). 3. Therapy to reduce cholesterol (sinvastatin) is recommended in high-risk patients (level 1). 4. Smoking cigarettes should be stopped (level 2). 5. Excessive alcohol use should be stopped, but small or moderate alcohol consumption may reduce the risk of stroke (level 1). 6. Regular physical activity is highly recommended (level 2). 7. It is recommended low sodium levels, low saturated fat levels, many fruits and vegetables and a diet rich with fiber (level 2). 8. Patients with increased body mass index (BMI) should be on a diet to reduce body weight (level 2). 9. Hormone therapy (estrogen / progesterol) should not be used in primary prevention of stroke (level 1).


Antithrombotic therapy There is no evidence that aspirin has been used in patients with asymptomatic internal artery stenosis, but such patients are at an increased risk of myocardial infarction, thus there is a consensus on the use of aspirin. Warfarin reduces the ratio of ischemic stroke by 70% in patients with atrial fibrillation (AF), with an optimal international normalized ratio (INR) between 2.0 and 3.0. In this group, aspirin (300 mg per day) reduces stroke by 21% and is significantly less effective than warfarin.

Recommendations 5.

1. Although aspirin does not reduce the risk of stroke in healthy people, it reduces the risk of MI and may be recommended to people who have one or more vascular risks (level 1). 2. Clopidogrel, ticlopidine, trifusal and dipyridamole are not tested in asymptomatic patients and therefore, they cannot be recommended for primary prevention of stroke (level 4). 3. Asymptomatic patients with internal carotid artery (ICA) stenosis greater than 50%, should receive aspirin to reduce the risk of MI (level 4). 4. The long-term oral anticoagulation therapy (target INR 2.5, between 2-3), should be considered in all AF patients at high risk of embolism: age > 75 years, or age > 60 years, and an additional riskâ&#x20AC;&#x201C;factor such as high pressure, left ventricular dysfunction and diabetes mellitus (level 1). 5. The long-term use of aspirin (325 mg per day) or warfarin is recommended in patients with/without valvular atrial fibrillation, at a moderate risk of embolism: age 60-75 years without additional risk-factors (level 1). 6. Warfarin is recommended for AF patients at the age of 60-75 with diabetes or coronary heart disease (level 1). 7. Although it is not yet determined in randomized studies, in patients over 75 years of age, warfarin may be used with a lower INR (target INR 2.0, between 1.6-2.5) to reduce the risk of haemorrhage (level 3). 8. AF patients who are unable to receive oral anticoagulant therapy should be offered aspirin (level 1). 9. The long-term use of aspirin (325 mg per day) or no therapy is recommended in patients with/without valvular atrial fibrillation at a low risk of embolism: age < 60 years without additional risk-factors (level 1). 10. AF patients who have prosthetic cardiac valves should receive long-term anticoagulation therapy with target INR (based on the type of prosthesis), provided that it is not less than INR 2-3 (level 2).


Carotid surgery and endovascular treatment of asymptomatic carotid stenosis Depending on the studied population, 15-20% of the ischemic strokes belong to the extracranial internal carotid artery stenosis. Two associations have presented evidence of carotid endarterectomy: “The American Academy of Neurology” and “The American Heart Association – professionals group of stroke council”, according to already implemented and completed studies, such as: “The North American Symptomatic Carotid Endarterectomy Trial (NASCET)” and “The European Carotid Surgery Trial (ECST)”.


SECONDARY PREVENTION Antithrombotic therapy Recommendations 6.

1. Appropriate antithrombotic therapy should be given as a prevention of recurrence of stroke and further vascular events (level 1). There are 3 treatment options, all of which can be considered as first choice depending on the patientâ&#x20AC;&#x2122;s characteristics. 2. Aspirin (50-325 mg) should be given to reduce the possibility of recurrence of stroke. 3. Wherever possible, a combination of aspirin (50 mg) and a slowly-releasing dipyridamole (200 mg twice a day) can be given as a first choice to reduce the risk of recurrence of stroke. 4. Clopidogrel is a bit more effective than aspirin in the prevention of further vascular events (level 1). 5. Also, it may be prescribed as a first choice or when aspirin and dipyridamole are not tolerated (level 4), as well as in high risk patients (level 3). 6. Patients with TIA or ischemic stroke and unstable angina pectoris should be treated with a combination of clopidogrel 75 mg and aspirin 75 mg (level 3). 7. Patients who begin treatment with thienopyridine derivatives should receive clopidogrel instead of ticlopidine because there are less side effects. 8. In patients who cannot be treated with aspirin or thienopyridine derivatives, slowly-releasing dipyridamole may be used as an alternative individually (200 mg twice a day) (level 3).


Anticoagula Oral anticoagulation (INR 2.0-3.0) reduces the risk of recurrence of stroke in patients with/without valvular atrial fibrillation or a recent ischemic stroke. Recommendations 7.

1. Oral anticoagulation (INR 2.0-3.0) is indicated after ischemic stroke and it is associated with AF (level 1). Oral anticoagulation is not recommended in patients with comorbid conditions such as fainting, epilepsy, severe demensia, or gastro-intestinal bleeding. 2. Patients who have prosthetic cardiac valves should receive long-term anticoagulant therapy with target INR between 2.5 to 3.5 or higher (level 2). 3. Patients with proven cardio-embolic stroke should be anticoagulated, if the risk of recurrence is high, with target INR between 2.0-3.0 (level 3). 4. Anticoagulation should not be used if there is no cardial embolism ischemic stroke, except in certain specific situations, like aortic atheroma, fusiform aneurysms of the basilar artery or dissection of the cervical artery (level 4).

Antihypertensive therapy Recommendations 8.

1. After a stroke or TIA, the blood pressure should be reduced, regardless of its level, with diuretics and/or ACE inhibitors, depending on the tolerance of the treatment (level 1). 2. The efficiency of other classes of medications for reducing the blood pressure has not been published yet by control studies.

Cholesterol reduction therapy Recommendations 9.

1. Patients with a history of ischemic stroke or TIA should be considered for statin therapy (simvastatin) (level 1).

Hormone therapy Recommendations 10.

.1. There are no indications for the use of hormone therapy for secondary prevention of stroke in the period after menopause in women (level 2).

Smoking Recommendations 11

1. All smokers should quit smoking, especially patients who have had a stroke (level 4).


Carotid endarterectomy (CEA Recommendations 12. 1. Conventional angiography, or one or, ideally, more of the following procedures: ultrasonography, MRA, or CTA â&#x20AC;&#x201C; may be used for identification and quantification of carotid artery stenosis. 2. CEA is performed in patients with stenosis from 70-99% without severe neurological deficits and with recent (<180 days) ischemic events. This is only valid for centers with pre-surgery complication rate (all strokes and mortality) of less than 6% (level 1). 3. CEA can be performed in certain patients with stenosis from 50-69% without severe neurological deficits. This is only valid for centers with pre-surgery complication rate (all strokes and mortality) of less than 6%. The group of patients which has most benefits from the surgery includes men with recent hemisphere symptoms (level 3). 4. CEA is not recommended for patients with stenosis less than 50% (level 1). 5. CEA should not be performed in centers which have a low rate of complications similar to those seen in NASCET or â&#x20AC;&#x153;European Carotid Surgery Trialists Collaborative Groupâ&#x20AC;? (level 1). 6. Patients should continue the antithrombotic therapy before, during and after the surgery (level 2). 7. Patients should be monitored by the appointed doctor and operator (level 4).

Carotid angioplasty and stenting

Recommendations 13.

1. Percutaneous transluminal carotid angioplasty and stenting may be performed in patients with contraindications of CEA or with stenosis at surgically inaccessible locations (level 4). 2. Percutaneous transluminal carotid angioplasty and stenting may be performed in patients with re-stenosis after initial CEA or stenosis after radiation (level 4). 3. Patients should receive a combination of clopidogrel and aspirin immediately before, during and at least one month after stenting (level 4).


Acute stroke management There are 5 basic points in the treatment of acute stroke. Treatment of a general condition that should be stabilized. Specific therapy directed against certain aspects of the pathogenesis of stroke or re-canalization of blood vessel occlusion or prevention of mechanisms leading to neuronal death in ischemic brain (neural-protection). Prophylaxis and treatment of complications that may be either neurological (such as secondary hemorrhage, occupying edema or seizures), or medical (such as aspiration, infections, decubitus ulcers, deep vein thrombosis or pulmonary embolism). Early secondary prevention, which aims to reduce the incidence of early recurrence of stroke.

Early rehabilitation. Pulmonary function or airway protection Normal respiratory function and adequate blood oxygenation are required for management of stroke, important for the prevention of metabolic functions in the ischemic penumbra.

Blood pressure management Monitoring of blood pressure and its treatment is crucial, because many of the patients with stroke have an increased blood pressure.


Table 8. Characteristics of selected antihypertensive medications which may be used in acute stroke.

Dose

Beginning (min.)

Duration

6-12.5 mg s.c

15-30

4-6

Reduction of cerebral blood flow, ortostatic hypotension

5-15

6-8

Deep hypotension, caution if given in combination with diuretics

1-5 2-5 1-2

1-2

1-10mg i.v.

1-2

3-6

Side effects of β- blocker (ex. bronchospasm, reduced heart output, bradycardia)

α/β-blocker Labetalol

20-80mg i.v. bolus 2mg/min i.v. инфузија

5-10

3-5

Vomiting, postural hypotension, nausea, dizziness.

β-blocker Urapidil

10-50mg i.v. bolus 9-30mg/h

2-5

3

0.075mg s.c.

5-10

3-5

Oral medications

Angiotensin-converting enzyme inhibitor Captopril Parenteral Central sympaticolytic Clonidine Vasodilators Nitroprusside Nitroglycerin Dihydralazin

β-blocker Propranolol

Central sympatholytic Clonidine

0.2mg првично после 0.1mg/h до 0.8mg 0.25-10µg/kg min-1 5-100µg/kg min-1 6.5-20mg i.v. bolus 1.5-7.5mg/h

Side effects

Nausea, vomiting, shivering of the muscles, sweating, thiocyanate intoxication. Tachycardia, headaches, vomiting. Tachycardia, headaches.

No serious side effects. The initial blood pressure increases, sedative effect..


Table 9. Suggested antihypertensive treatment in acute ischemic stroke

1. 1. Systolic blood pressure 180-220 mm Hg/ or diastolic blood pressure 105-140 mm Hg

Not to be treated

2. Systolic blood pressure >=220 mm Hg/ or diastolic blood pressure 120-140 mm Hg in repetitive measuring

Captopril 6.25-12.5 mg p.o/i.m Labetalol 5-20 mg i.v Urapidil 10-50mg i.v следено од 4-8mg/h i.v. Clonidine 0.15-0.3 mg i.v. или s.c. Dihydralazine 5mg i.v. плус metoprolol 10 mg

2. 3. Diastolic blood pressure >= 140 mm Hg

Nitroglycerin 5 mg i.v. следено од 1-4mg/h i.v. Sodium nitroprusside 1-2 mg


Glucose metabolism An increased level of serum glucose during admission in hospital may frequently be found due to previously known or unknown diabetes. A high level of glucose is harmful for a stroke. Recommendations 14

1. Continuous cardiac monitoring is recommended within the first 48 hours from the occurrence of stroke, especially in patients who: a) have previously known cardiac disease, b) history of arrhythmias, c) unstable blood pressure, d) clinical signs/symptoms of heart failure, e) abnormal ECG at the beginning and f ) infarction involving insular cortex. 2. Monitoring oxygenation with pulse oxymeter is recommended. 3. O2 administration is recommended in cases with hypoxemia (blood gas analyses O2 <92%) 4. Intubation is recommended in cases with potential reverse respiratory insufficiency. 5. Routine blood pressure reduction is not recommended, except in extremely increased values (>200-220 mm Hg systolic or 120 mm Hg diastolic pressure for ischemic stroke, >180/105 mm for haemorrhagic stroke) confirmed with several repeatable measurements. 6. An immediate antihypertensive therapy for a more moderate hypertension is recommended in cases with stroke and heart failure, aortic dissection, acute myocardial infarction, acute renal failure, thrombosis or intravenous heparin, but it should be given with caution. 7. Recommended target blood pressure in patients 1) with previous hypertension 180/100-105 mm Hg 2) without previous hypertension 160-180/90-100 mm Hg and 3) in thrombosis avoid systolic pressure over 180 mm Hg. 8. Recommended medications for blood pressure treatment: 1) intravenous labetalol or urapidil and 2) intravenous sodium nitroprusside, nitroglycerin or oral captopril. 9. Avoid Nifedipine and other medications for drastic pressure reduction. 10. Avoid and treat hypotension especially in unstable patients by administrating an adequate dose of liquids and when necessary, volume magnifiers and/or catecholamine (epinephrine 0.1-2 mg.h plus dobutamine 5-50 mg/h). 11. Monitoring the level of serum glucose is recommended, especially in patients- diabetics. 12. Glucose solutions are not recommended because of detrimental effects of hyperglycemia. 13. Treatment of the level of serum glucose >10 mmol/l with titration of insulin is recommended. 14. An immediate correction of hypoglycemia is recommended with intravenous dextrose bolus or infusion of 10-20% glucose. 15. Treatment of body temperature >=37.5 is recommended. 16. In case of cold, a search for a possible infection is recommended, in order to begin with an adequate antibiotic therapy. 17. Antibiotic, antimycotic or antiviral prophylaxis is not recommended in immunocompetent patients. 18. Monitoring and correction of electrolytes and fluid disorders are recommended. 19. Hypotonic solutions (NaCl 0.45% or glucose 5%) are counter indicators because of a risk of increasing of the brain edema resulting from reduced plasmic osmosis.


SPECIFIC TREATMENT Recommendations 15.

1. Intravenous rtPA (0.9 mg/kg, max 90 mg), with 10% of the dose given as bolus followed by infusion lasting 60 min., is a recommended treatment in the first 3 hours of the beginning of ischemic stroke (level 1). 2. The benefit from the use of intravenous rtPA for acute ischemic stroke over 3 hours after the onset of the symptoms is smaller, but it is shown even up to 4.5 hours. (level 1). 3. Intravenous rtPA is not recommended when the time of the beginning of the stroke cannot be precisely determined, this includes people whose strokes are recognized after waking up (level 4). 4. Intravenous giving of streptokinase is dangerous and is not recommended for use in people with ischemic stroke. 5. Data on the efficacy and safety of any intravenously given thrombolytic medication are not available to recommend. 6. Intra-arterial treatment of acute MCA occlusion within a period of 6 hours with the use of pro-urokinese leads to a significantly improved result (level 2). 7. Acute basilar occlusion may be treated with intra-arterial therapy in selected centers within institutional protocol as an experimental therapy or in multi-centric clinical studies (level 4). 8. At the moment Ancrod cannot be recommended for use in acute ischemic stroke outside the terms of a clinical study.

Recommendations 16.

1. Aspirin (100-300 mg per day) may be given in 48 hours after ischemic stroke (level 1). 2. If a thrombin therapy is planned, aspirin should not be given. 3. Aspirin is not allowed for 24 hours after thrombin therapy. 4. There are no recommendations for the general use of heparin, low molecular heparin or heparinoids after ischemic stroke (level 1). 5. A whole dose of heparin may be used when there are selected indications like heart resources with a high risk of re-embolisation, arterial dissection, or a high level of arterial stenosis before surgery (level 4). 6. Haemodilution therapy is not currently recommended for managing patients with acute stroke (level 1). 7. At the moment, there are no recommendations for treatment of patients with stroke using neuro-protective substances (level 1).


Prevention and treatment of complications Acute stroke has predisposition to medical complications such as pneumonia, urinary tract infections, malnutrition or volume depletion. Patients may also suffer from deep vein thrombosis and pulmonary embolism. Early support care and monitoring of the physiological parameters may prevent such complications. This is best performed in dedicated stroke departments that have an experienced team and early mobilization. Immobility may lead to infections, contractions and decubitus. Recommendations 17.

1. A low dose of subcutaneous heparin or low molecular heparin should be considered only for patients at high risk of DVT or pulmonary embolism (level 2). 2. The incidence of vein thromboembolism may be reduced through re-hydration and mobilization and ranked compression socks (level 4). 3. Infections after stroke should be treated with adequate antibiotics. 4. Respiratory pneumonia may possibly not be prevented with nasogastric feeding. 5. Early mobilization helps to prevent a number of complications after a stroke, including respiratory pneumonia, DVT and decubitus (level 4). 6. Giving anticonvulsants to prevent repetitive attacks is highly recommended (level 3). 7. Giving prophylaxis of anticonvulsants to patients with recent stroke who have not had attacks is not recommended (level 4).

Brain edema and increased ICP Ischemic brain edema occurs during the first 12-24 hours after the occurrence of stroke and it is the main reason for an early or late clinical deterioration. The most serious situations are those in young patients with complete MCA infarction, where the brain edema and the increased ICP may lead to hernia within 2-4 days after the onset of the symptoms, and to death in about 80% of the cases with standard treatment.

Medical therapy Basic management of increased ICP after stroke includes placing the head in a position higher than 30째, avoiding harmful stimuli, relief of pain, adequate oxygenation and normalization of the body temperature. If ICP monitoring is possible, the cerebral perfusion pressure should be retained >70 mm Hg. Although there is a lack of strong evidence, osmotherapy with 10% glycerol is usually given intravenously or intravenous mannitol 25-50 g every 3-6 hours is the first medical treatment which is used if clinical and/or radiological signs of space-occuring edema appear. Hypertonic saline solution given intravenously must be similarly effective, although the data currently available are not definitive. Hypotonic solution containing glucose should be avoided as a fluid replacement. Dexamethasone and corticosteroids are not useful for treatment of brain edema after stroke.


REFERENCES Antiplatelet trialistsâ&#x20AC;&#x2122; collaboration: collaborative meta-analysis of randomized trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324:71-86 The management of combined coronary artery disease and peripheral vascular disease. Cassar A. et al. Eur. Heart J., July 1, 2010; 31(13):1565-1572 Recommendations for the outpatient surveillance of renal transplant recipients. Kasiske B.L. et al. J. Am. Soc. Nephrol, Oct. 1, 2000; 11 (90001): S1-S86. Contemporary Management of Carotid Stenosis: Carotid Endarterectomy Traditionally Been Underestimated?: Significance of Reperfusion Hemodynamics. Bailey D.M. et al. Stroke, June 1, 2007; 38(6): 1946-1948. Reanalysis od the final results of the European carotid surgery trial. Rothwell P.M. et al. Stroke, Feb 1, 2003; 34(2):514523. Transient Ischemic Attack. Johnston S.C. N. engl. J. Med., Nov.21, 2002; 347 (21):1687-1692. Carotid endarterectomy in elderly patients: low complication rate with overnight stay. Salameh J.R. et al. Arch Surg, Nov. 1, 2002; 137(11):1284-1287.


APPENDIX

Listed below are tools that are often used for pre-hospital assessment of stroke, as well as tools for evaluation of acute condition. Cincinnati Prehospital Stroke Scale Los Angeles Prehospital Stroke Scale NIH Stroke Scale

“Cincinnati Prehospital Stroke Scale” Name and Surname of the patient:______________________________________________ Date: _____________________ Facial droop  Normal: Both sides of the face move equally.  Abnormal: One side of the face does not move at all.

Arm drift – Движење на рацете  Normal: both arms move normally or they are at peace.  Abnormal: one arm moves uncontrollably, differs from the other.

Speech  Normal: the patient pronounces words correctly, with no ambiguities  Abnormal: unclear speech or incorrect words or no words spoken at all


“Los Angeles Prehospital Stroke Screen (LAPSS)” Name and Surname of the patient:_______________________________________________________________ Date: _ _____________________ SCREENING CRITERION Yes No Age over 45 years.   Without previous history of seizure disorder   New manifestation of neurological symptoms within the last 24 hours.   The patient has been hospitalized at the beginning (before the event) Glucose between 60-400   Test: search visible asymmetry Normal Right Left Smile/grimace   weakness  weakness Фат   weak  weak  no grip  no grip Weakness of the arms   moving down  moving down  falling immediately  falling immediately Based on the test, the patient has only unilateral (not bilateral) weakness: Yes  No  If the answer to all the questions above is yes (or unknown), LAPSS screening criterion is met:  Yes  No If the LAPSS criterion for stroke is met, call the hospital with “CODE STROKE”, if not, then return to the adequate treatment protocol. (Note: The patient may still experience stroke, even if the LAPSS criterion has not been met.)


SUDDEN WEAKNESS SUDDEN DIZZINESS

SUDDEN SPEAKING PROBLEMS

SUDDEN EYESIGHT PROBLEMS SUDDEN HEADACHE


CONTEMPORARY DIAGNOSTICAND TREATMENT OF PATIENTS WITH STROKE