SPREAD V Ed.

Acute stroke:
hospital admission (treatment)

 
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Collaborations
Authors
Introduction
Methodology
Epidemiology
Diagnostic work-up
Risk factors
Primary prevention
Acute stroke: pre-hospital
Acute stroke: diagnosis
Acute stroke: treatment
Acute stroke: steady-state
Secondary prevention
Surgical treatment
Organising rehabilitation
Rehabilitation
Post-stroke sequels
Juvenile-uncommon causes

Acute stroke:
hospital admission (treatment)

R 10.1
Grade A

 Intravenous administration of streptokinase is not recommended.
R 10.2
Grade A		 The treatment with intravenous r-tPA (0.9 mg/kg, maximum 90 mg, with 10% of the dose given as a bolus followed by an infusion lasting 60 min) is recommended within 3 h of onset of ischaemic stroke in the eligible patients according to the product technical sheet.
S 10–1 There is still some dissent concerning the grade to be attributed to the above recommendations, which cannot be influenced by the otherwise important results of the SITS-MOST, which was not a RCT. Clinical Evidence in its June 2007 release, accounting for the results of the systematic reviews on thrombolysis where a definite statistical heterogeneity was seen (I2=62%) that make not fully reliable the results favourable to the treatment, continues to classify the treatment as “trade-off between benefit and harm”, and specifies that the treatment decreases dependence among survivors but increases total mortality and fatal haemorrhages. For these reasons "B" should be considered a more appropriate grade for Recommendation 10.2.
S 10–2 The benefit from the use of intravenous r-tPA for acute ischaemic stroke beyond 3 h after onset of the symptoms is smaller, but present up to 4.5 h. When r-tPA is administered between 4.5 and 6 h of stroke onset, only a statistically non-significant trend towards effectiveness is obtained.
A double-blind, randomised, placebo-controlled trial denominated ECASS III (European Cooperative Acute Stroke Study) is in progress to evaluate efficacy and safety of r-tPA whint 3-4 hours from an acute ischaemic stroke.
Another ongoing double-bind, randomised, placebo-controlled trial, denominated IST 3, is estimating in a large population of patients with acute ischaemic stroke the risk-to-benefit ratio of the administration of r-tPA within 6 h of onset. This trial also evaluates efficacy and safety in patients >80 years of age.
S 10–3

Thrombolysis should be performed in selected centres that are appropriately equipped to carry out the treatment within the due time limits and have the facilities for a close neurological and blood pressure monitoring during the 24 hours after treatment.

S 10–4

The evidences justifying the endovascular treatment are limited and include the results of PROACT I and II and several small clinical series, partly uncontrolled. The fast technological advances concerning to techniques and devices, as well as the variable operators’ ability prevented additional controlled trials. From the current evidence, these techniques are probably more effective on the occlusion of major arterial vessels but at the expense of greater difficulties and organisational costs and with a risk for the individual patient that cannot adequately be quantified.

S 10–5

The device defined MERCI (Mechanical Embolus Removal in Cerebral Ischemia) Retrieval to mechanically remove the obstruction from the major cerebral arteries was approved by the FDA in the USA and received the EC mark in the European Union. The benefits from its use in clinical practice are still to be unequivocally demonstrated.

S 10–6

Centres with proven expertise in endovascular neurological procedures can consider the endovascular approach in case of: a. contraindication to i.v. thrombolysis; b. inefficacy of the i.v. treatment.

R 10.3
Grade D		 Endovascular techniques using thrombolytic agents associated or not with mechanical manoeuvres (angioplasty, thromboaspiration, thrombus retrieval) are indicated in centres with expertise in interventional neuroradiology, in case of occlusion of major arterial vessels (internal carotid, principal segment of the medial cerebral artery, basilar artery) with clinical presentation predictive of a high risk of death or severe functional outcome.
R 10.4
Grade D		 Intra-arterial thrombolysis, even after 6 h of stroke onset, is recommended for documented basilar artery occlusion in centres with expertise in interventional neuroradiology.
Within 3 hours from onset, the i.v. thrombolysis is anyway indicated.
S 10–7 In patients with venous sinus thrombosis, when intravenous heparin therapy is ineffective, thrombolysis may be an optional treatment.
R 10.5
Grade A		 Aspirin (160-300 mg per day) is recommended in all patients with acute stroke unless anticoagulant therapy or thrombolysis are indicated.

®GPP

 According to the SPREAD Collaboration the dose of 300 mg/daily is the most adequate in the acute stroke phase.
S 10–8 The i.v. treatment with heparin represents the prevailing choice for patients with large arteries dissection and is proposed by international experts' groups for sub-occlusive stenoses prior to surgery. Since, however, conclusive evidences are still missing, the SPREAD Collaborations suggest the anticoagulant treatment as general indication, to be individually evaluated.
R 10.7
Grade D		 Anticoagulant therapy with intravenous heparin is recommended for the treatment of venous sinus thrombosis.
R 10.8 a
Grade A		 The use of neuroprotective drugs is not recommended for the treatment of acute ischaemic stroke.
R 10.8 b
Grade A		 Corticosteroids are not recommended for the treatment of acute ischaemic stroke.
R 10.8 c
Grade A		 Osmotherapy (mannitol, glycerol) is not recommended for the general treatment of acute ischaemic stroke. For the treatment of life-threatening brain oedema after stroke see recommendation 11.31 b.
S 10–9 The choice of the antithrombotic agent for early secondary prevention of stroke should be made according to the pathogenic subtype of stroke (to be determined within 48 h of onset), to the severity of stroke, and to the potential patient’s compliance with the treatment. The choice should also account for the clinical severity, the anticipated patient’s compliance and the possibility to adequately monitor the patient if needed, such as during oral anticoagulant therapy.
R 10.9 a
Grade A		 In patients with non-valvular atrial fibrillation, oral anticoagulation is recommended with a target INR between 2.0 and 3.0.
R 10.9 b
Grade D		 In patients with other cardio-embolic sources and a high risk of early stroke recurrence, the administration of full-dose i.v. heparin (target PTT 1.5-2.5 times the basal value) followed by oral anticoagulation (target INR between 2.0 and 3.0 in heart valvular diseases with or without AF, and between 2.5 and 3.5 in presence of mechanical prosthetic valves) is recommended.
S 10-10 In patients with non-valvular AF, transoesophageal echocardiography may reveal high cardio-embolic risk conditions such as left atrial thrombus, dense spontaneous echo contrast, decreased flow velocity in the left atrial appendage, atheroma of the aortic arch. These patients should be considered at high risk of early re-embolism, but at present there is no evidence from randomised studies about the best anticoagulation approach (type of agent and timing).
R 10.10
Grade D		 In patients with any type of cardioembolic stroke, in absence of the contraindications listed in Chapter 12, it is indicated to begin the oral anticoagulant treatment between 48 hours and 2 weeks, taking into account:
clinical severity;
size of the lesion shown by neuroimages;
cardiological comorbidity (determined also with the aid of echocardiography).
R 10.11
Grade B		 In patients with cardio-embolic stroke unable to receive oral anticoagulants, aspirin 325 mg per day is recommended for the early secondary prevention of stroke.
R 10.12
Grade D		 In patients with cardio-embolic stroke while on oral anticoagulation for atrial fibrillation and with INR values below optimal range, anticoagulation therapy is recommended according to recommendation 10.10.
R 10.13
Grade D		 In patients presenting with cardio-embolic stroke who have a prosthetic heart valve and are being treated with an adequate anticoagulation regimen, the supplementation of oral anticoagulation with an antiplatelet agent is recommended.
S 10-11 In patients with acute stroke and patent foramen ovale, therapeutic choices for secondary prevention are the same as those recommended for long-term therapy (see recommendation 12.13 a, b, c), and timing is that indicated in recommendation 10.10.
R 10.14
Grade A		 In patients with stroke secondary to atherothrombosis of extracranial vessels who were not on antithrombotic therapy, aspirin is recommended .

®GPP

 For the acute phase, the SPREAD Collaboration recommends a dose of 300 mg per day.
S 10-12 In case of recurrent ischaemic stroke in patients already under aspirin therapy, it is appropriate:
bulletre-evaluate the aetiopathogenesis of the event;
bulletverify the patient's compliance and possible negative interactions (e.g., concurrent use of NSAIDs);

and then:

bulletincrease the dose of aspirin, or
bulletcontinue with aspirin, intensifying the other measures of secondary preventions (e.g., introducing a statin), or
bulletuse a different antiplatelet or a combination of drugs (see Recommendation 10.15).
R 10.15
Grade D		 In patients with stroke secondary to atherothrombosis of extracranial vessels who have a recurrent event while on aspirin treatment, ticlopidine (250 mg bid, assessing blood cells count twice monthly for the first 3 months) or clopidogrel (75 mg per day), or dypiridamole slow release (200 mg bid) combined with aspirin (25 mg bid) is recommended.
S 10-13 In patients with stroke secondary to atherothrombosis of extracranial vessels who exhibit repeated recurrent events in spite of adequate antiplatelet treatment, the oral anticoagulant therapy is a reasonable alternative, along with the adequate control of risk factors.
S 10-14 There is no consistent evidence about the effectiveness of antithrombotic versus anticoagulation therapy in patients with aortic atheroma. On a theoretical basis, they should be treated like those with atherothrombosis of extracranial arteries, but data reported in the literature are in favour of anticoagulation.
S 10-15 In patients with lacunar stroke, secondary prevention treatment should be decided after investigating all potential causes of stroke, including atherothrombosis and cardio-embolism.
R 10.16
Grade B		 In patients at high risk of deep venous thrombosis (DVT) (i.e. presenting with plegic limbs, or reduced consciousness, or obesity or previous lower-limb venous diseases) prophylaxis with subcutaneous low-dose heparin (5000 i.u. twice daily) or low-molecular-weight heparins is recommended starting since hospital admission.
S 10-16 In patients at low risk of DVT, systematic prophylaxis with heparin has an unfavourable risk-to-benefit ratio considering the risk of intra- and extra-cerebral haemorrhagic complications.
R 10.17
Grade D		 Early mobilisation and hydration are always indicated to prevent DVT. Graded  compression stockings as well as intermittent pneumatic compression are recommended for DVT prevention in combination with anticoagulation or as an alternative when anticoagulation is contra-indicated.
S 10-17 There are no evidences supporting the use of anticoagulants in progressing stroke. Based on the recommendations of some international panel, their use may be indicated only in case of subocclusive carotid or basilar stenosis or of basilar occlusion, individually evaluating their application.
S 10-18 For the prevention and treatment of progressing stroke, monitoring and adequate treatment of hyperthermia, hyperglycaemia and brain oedema are advisable.
R 10.18
Grade C		 During the first 15 days of treatment with heparin, regular monitoring of platelet count is recommended.
R 10.19
Grade D		 Immediate cessation of treatment with heparin is recommended in case of heparin-induced thrombocytopenia (proven or suspected). In patients with heparin-induced thrombocytopenia, oral anticoagulation is not recommended as an alternative.
R 10.20
Grade D		 In patients who were already on adequate oral anticoagulation, the continuation of oral anticoagulants is recommended after cessation of heparin.
R 10.21
Grade D		 In patients with heparin-induced thrombocytopenia, therapy with hirudin, or dermatan sulphate, or danaparoid, or thrombolytic agents is the recommended alternative treatment. Oral anticoagulation may be started as soon as the platelet count recovers.
R 10.22
Grade D		 Brain CT is recommended as first choice test for diagnosing a cerebral haemorrhage in the acute setting.
R 10.23
Grade D		 Angiography is recommended in patients with intraparenchymal haemorrhage without a definite cause, who are candidate to surgical intervention. This applies in particular to patients with haemorrhage in an atypical location, young, normotensive and clinically stable.
R 10.24
Grade D		 Angiography is not recommended in elderly and hypertensive patients, with haemorrhage located in the basal and thalamic ganglia, in whom CT does not suggest the presence of a structural lesion.
R 10.25
Grade D		 MRI and MRA are useful in selected cases of intraparenchymal haemorrhage, and are indicated in patients with lobar lesions and negative angiography who are candidates to surgery, for the diagnosis of cavernous angioma or in patients in whom amyloid angiopathy is suspected.
R 10.26
Grade D		 In patients with intracranial haemorrhage, the treatment of arterial hypertension is recommended:
if systolic pressure is >200 mm Hg or mean pressure is >150 mm Hg, treatment with nitroprusside or urapidil should be initiated and monitored every 5 minutes;
if systolic pressure is >180 mm Hg or mean pressure is >130 mm Hg and there is evidence or clinical suspicion of high intracranial pressure, consider the monitoring of intracranial pressure and the decrease of blood pressure but - keeping the cerebral perfusion between 60 and 80 mm Hg - initiate an intravenous therapy with labetalol, urapidil, nitroprusside or furosemide or low doses of other drugs that can be given intravenously;
if systolic pressure is >180 mm Hg or mean pressure is >130 mm Hg but there is no indication of intracranial hypertension, consider a modest decrease of blood pressure (target 160/90 mm Hg, mean pressure around 110 mm Hg) with i.v. therapy in bolus or continued administration of anti-hypertensive agents, and re-evaluate the patient every 15 minutes.
R 10.27
Grade D		 The antiepileptic prophylaxis is not recommended in patients with intraparenchymal cerebral haemorrhage.
R 10.28
Grade D		 External catheters of ventricular derivation should not be maintained longer than 7 days.
R 10.29
Grade D		 For the treatment of endocranial hypertension, the following options are recommended:
bulletosmotic agents:
the first substances to be used, but not for prophylaxis, i.v. mannitol 20% (0.25 to 0.5 g/kg for 4 hours) or glycerol (250 mL of 10% glycerol in 30-60 min every 6 hours) - this alternatively per os (50 mL of 10% solution every 6 h) - are to be reserved for patients with elevated endocranial hypertension, rapid clinical deterioration, oedema surrounding the haemorrhage. Due to the known rebound effect, they have to be used for less than 5 days. During therapy with osmotic agents, sodium levels and haematology should be systematically controlled since they may induce haemolysis.
 
bulletfurosemide:
at the dose of 10 mg every 2-8 h it can be administered along with osmotic therapy. Plasma osmolarity should be monitored twice daily in patients on osmotic therapy, and levels <310 mOsm/L should be maintained.
 
bullethyperventilation:
hypocapnia causes cerebral vasoconstriction, almost immediate decrease of cerebral flow and decreased endocranial pressures after 30 min. A decrease of pCO2 to 30-35 mmHg can be obtained with constant ventilation using a volume of 12-14 mL/kg and reduces the endocranial pressured by 25%-30%.
 
bulletsedative agents:
neuromuscular paralysis combined with adequate thiopental sedation prevents the increase in intrathoracic pressure by vomiting, cough, resistance to the ventilator. Under these circumstances, non-depolarising agents such as vecuronium or pancuronium are to be preferred.
 
R 10.30
Grade D		 Steroids are not indicated in the treatment of endocranial hypertension.
R 10.31
Grade D		 In patients with intraparenchymal haemorrhage and risk of deep vein thrombosis, the prevention with elastic stockings or mechanical means or both, more effective than the elastic stockings alone, are recommended. After 4-5 days from the haemorrhage onset, the use of LMWH or unfractioned heparin at prophilactic doses can be considered.
S 10-19 There is insufficient evidence on the safety, in the post-acute period, of the treatment with low-dose heparin or aspirin for the prevention of deep vein thrombosis in patients with intraparenchymal haemorrhage).
R 10.32
Grade D		 In patients with cerebral haemorrhage during anticoagulant treatment, the rapid correction of haemostasis is recommended. Depending on the therapy applied, it can be achieved with vitamin K, prothrombin preparation or fresh plasma (for oral anticoagulants), with platelet concentrates and cryoprecipitates (for the fibrinolytic therapy with r-tPA) or with protamine sulphate (for i.v. heparin).
S 10-20 The evidences on the surgical indications in case of spontaneous intracerebral haemorrhage were recently increased upon the STICH study results. In this study, performed on a large number of patients randomised to early neurosurgical treatment or initially conservative treatment (up to possible clinical deterioration), no superiority of either approach was seen in terms of benefit. In the supratentorial spontaneous haemorrhage, no superiority of early surgical treatment vs. conservative treatment was seen.
R 10.33

Surgical management of intracerebral haemorrhage is recommended in patients with:
10.33 a
Grade D
cerebellar haemorrhage larger than 3 cm and neurological deterioration or signs of brainstem compression and hydrocephalus;
10.33 b
Grade D
moderate (≥30 and <50 cm3) to large lobar haemorrhage (≥50 cm3), with progressive neurological deterioration;
10.33 c
Grade D
intracerebral haemorrhage due to surgically accessible aneurysms or arteriovenous malformations.
R 10.34 Surgical management of intracerebral haemorrhage is not recommended:
10.34 a
Grade C
as early systematic treatment of cerebral haemorrhages by any surgical technique unless neurological deterioration is present;
10.34 b
Grade D
for small haemorrhages (<10 cm3) or minimal neurological deficits (to be treated medically);
10.34 c
Grade D
in patients with GCS ≤4 (owing to high mortality and poor surgical outcome);
10.34 d
Grade D
for intracerebral haemorrhage due to non surgically-accessible aneurysms or arteriovenous malformations
S 10-21

The elements in favour of the surgical treatment of an unruptured aneurysm include: young age (long life expectation with increased cumulative risk of rupture), history of SAH from another aneurysm, familiarity for SAH and/or aneurysms, diameter greater than 7 mm, symptoms of compression or evidence of progressive enlargement, localisation on the median line (aneurysm of the anterior communicating or of the basilar artery).
S 10-22 The aneurysms of the intracavernous portion have to be considered separately, having a limited bleeding risk even if symptomatic. The intervention may become necessary more because of compressive symptoms, rather than for the bleeding risk.
R 10.35
Grade D

In a patients who had a SAH from another aneurysm, the endovascular or surgical treatment of unruptured aneurysms is recommended because of their risk of rupture regardless of their dimension.
R 10.36
Grade D		 The endovascular or surgical treatment of symptomatic aneurysms is recommended because of their high probability of rupture, or of causing progressive symptoms or embolisms.
R 10.37
Grade D		 The treatment of large (>7 mm) aneurysms is recommended. Recent data indicate a lower morbility and mortality among patients treated by endovascular procedures, but better complete occlusion after surgical treatment. The endovascular treatment is indicated in presence of specific risk conditions (advanced age, severe medical or neurological conditions).
R 10.38
Grade D		 Small (<7 mm) aneurysms in patients without history of SAH or familiarity can be treated conservatively. However, it is recommended to monitor whether dilation of conformational changes occur along the time.
R 10.39
Grade D		 For the emergency diagnosis of SAH, cerebral CT without contrast media is recommended.
R 10.40
Grade D		 In presence of clinical suspicion of SAH with negative CT, the lumbar puncture is recommended, even only to exclude this pathology.
R 10.41
Grade D		 In patients with SAH, digital angiography is recommended, since it still represents the best standard for the morphological description of the aneurysm.
R 10.42
Grade D		 MRA and CTA are recommended in patients with SAH when digital angiography cannot be performed.
R 10.43
Grade D		 The endovascular intervention is recommended also in case of small-medium size unruptured aneurysms.
S 10-23 Advanced age, intermediate and high clinical grading (Hunt and Hess grades 3-4) after subarachnoid haemorrhage, and specifically the aneurysms of the posterior circulation, of difficult surgical access regardless of whether ruptured or unruptured, are factors that, all other indications being equal, direct the therapeutic choice toward the endovascular intervention.
R 10.44
Grade D		 The surgical treatment of aneurysms in SAH is recommended when the aneurysm canneral vascular conditions) and in presence of cerebral haematoma causing compot be treated by endovascular approach (due to morphology, anatomy or genression.
R 10.45 a
Grade D		 The endovascular or surgical treatment of aneurysms in SAH is recommended within 72 hours from onset.
R 10.45 b
Grade D		 Careful monitoring of the evolution and endovascular re-treatment of partially closed aneurysms is recommended, since they have a high risk of bleeding.
S 10-24 The treatment of SAH due to aneurysms is indicated within 72 hours from onset. Data on mortality, disability, neurological complications are in favour of the endovascular treatment, which, however, has a greater proportion of incomplete closures and a higher proportion of early re-bleedings, to be verified on the medium-long term.
R 10.46
Grade D		 The closure of the afferent vessel in patients with SAH is recommended, after an occlusion test, when the direct surgical or endovascular closure of the aneurysm is impossible.
S 10-25 There is no evidence if favour of the efficacy of bed confinement in patients with SAH and of the anti-hypertensive therapy in the acute setting to prevent the re-bleeding of the aneurysm. However, the administration of anti-hypertensive agents is frequently applied.
S 10-26 The anti-fibrinolytic therapy to prevent re-bleeding in patients with SAH can be used under special circumstances. These encompass patients with reduced risk of vasospasm who are candidate to delayed surgical treatment. It is not a routine treatment since it causes cerebral ischaemia in a proportion similar to that of the re-bleeding episodes avoided.
R 10.47
Grade C		 Endovascular or surgical clipping of the ruptured aneurysm is recommended to decrease the proportion of re-bleeding after SAH.
R 10.48
Grade D		 The endovascular treatment, or the surgical ligature of the afferent vessel after occlusion test, may be recommended in case of aneurysms untreatable with direct approach, in presence of progressing neurological symptoms of increasing aneurysm size.
S 10-27 The aneurysms treated with intraluminal spirals require a control in the 2 following years to monitor possible re-canalizations that require a re-intervention.
R 10.49
Grade D		 The trans-cranial Doppler is recommended to diagnose and monitor the vasospasm.
R 10.50
Grade D		 Hypertension, hypervolaemia and haemodilution, statins and magnesium sulphate are recommended to prevent and treat vasospasm. However, their efficacy was not univocally demonstrated.
R 10.51
Grade C		 Oral nimodipine is recommended for the treatment of post-SAH vasospasm. If oral administration is impossible, the i.v. administration may be indicated.
S 10-28 The removal of basal clots during intervention, the cisternal administration of thrombolytic agents or the administration of anti-inflammatory or anti-oxidant agents is of questionable efficacy to prevent the vasospasm post-SAH.
R 10.52
Grade D		 Intravascular angioplasty is recommended in patients with post-SAH vasospasm, in whom the other treatments were found ineffective.
R 10.53
®GPP		 In the event of acute hydrocephalus after SAH with reduced conscience, the ventricular derivation treatment is recommended, even if it increased the risk of re-bleeding and infectious complications can occur.
S 10-29 The occurrence of chronic hydrocephalus is frequent after SAH and can be treated with ventricular-peritoneal or ventricular-cardiac derivation if the patient is symptomatic.
R 10.54
Grade D		 In patients with acute stroke, high-grade symptomatic stenosis or ipsilateral acute carotid thrombosis and crescendo TIAs or progressing stroke, emergency carotid endarterectomy (CEA) is recommended, in expert centres with perioperative complication rate of less than 3%.
S 10-29
a. Risk models ought to be employed to select the patients for the emergency CEA,
b. Currently there is no evidence on the risk/benefit ratio of the emergency CEA in patients with progressing or acute (within 6 h) stroke even if associated with critical stenosis or acute carotid thrombosis.

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