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Acute management of ischaemic stroke 2012
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Early Early Management of Management of Ischemic StrokeIschemic Stroke
DR SANJAY JAISWAL, MD,DMDR SANJAY JAISWAL, MD,DM
Member world stroke Member world stroke organizationorganization
Consultant NeurologistConsultant Neurologist
Jaiswal Hospital and Neuro Jaiswal Hospital and Neuro InstituteInstitute
Kota ,Rajasthan.Kota ,Rajasthan.
ReferenceReference
Guidelines for the Early Guidelines for the Early Management of Adults With Management of Adults With Ischemic Stroke Ischemic Stroke Stroke Stroke 2007;38;1655-17112007;38;1655-1711
Acute ischemic stroke Acute ischemic stroke N Engl J N Engl J Med 2007; 357:572-579, Aug 9, Med 2007; 357:572-579, Aug 9, 2007 2007
Brain Attack!Brain Attack! Acute stroke = ‘brain Acute stroke = ‘brain
attack’attack’ Every minute matters: Every minute matters:
‘time is brain’‘time is brain’ Combat therapeutic Combat therapeutic
nihilismnihilism
Time is Brain…why?Time is Brain…why?The typical patient loses 1.9 million The typical patient loses 1.9 million
neurons each minute in which stroke is neurons each minute in which stroke is untreateduntreated
The ischaemic penumbraThe ischaemic penumbra
WHO DEFINITION OF WHO DEFINITION OF STROKESTROKE
A NEUROLOGICAL DEFICIT OFA NEUROLOGICAL DEFICIT OF SuddenSudden onset onset WithWith focal focal rather than global rather than global
dysfunctiondysfunction In which, after adequate In which, after adequate
investigations, symptoms are investigations, symptoms are presumed to be of non-traumatic presumed to be of non-traumatic vascular originvascular origin
and last for and last for >24 hours>24 hours
New definition of TIANew definition of TIA A brief episode of neurological A brief episode of neurological
dysfunction caused by focal brain or dysfunction caused by focal brain or retinal ischaemia with clinical retinal ischaemia with clinical symptoms lasting less than one hour symptoms lasting less than one hour without evidence of infarctionwithout evidence of infarction
Types of StrokeTypes of Stroke
85% Ischemic
15 % hemorrhagic
•Language loss (aphasia)•Right hemiparesis•Right hemisensory loss•Right visual field cut•Left gaze preference
Left MCA SyndromeLeft MCA Syndrome
Right MCA SyndromeRight MCA Syndrome•Left hemi-neglect
visual,spatial,•Left hemiparesis•Left hemisensory loss•Left visual field cut•Neglect of deficits
“anasgnosia”
Stroke is due to sudden vascular Stroke is due to sudden vascular occlusionocclusion
ACA
MCA
•50-70% of all stroke is due to embolism (cardiogenic and artery-to-artery) •80 % of acute strokes are due to MCA territory ischemia• Arterial occlusion is seen in 80-90% within 6-24° of symptom onset• Spontaneous recanalization seen in ~ 20% within 6 ° of symptoms
Vascular occlusion causes stroke Vascular occlusion causes stroke symptomssymptoms
Stroke Risk Factors Non-Stroke Risk Factors Non-modifiablemodifiable
AGEAGE Gender -maleGender -male Race – Blacks > Asians or Race – Blacks > Asians or
Hispanics> Hispanics> WhitesWhites Family Hx. Family Hx. Coagulation DisordersCoagulation Disorders Cardiac Disease Cardiac Disease
Stroke Risk Factors ModifiableStroke Risk Factors Modifiable
HypertensionHypertension Diabetes mellitusDiabetes mellitus HypercholesterolemHypercholesterolem
iaia Elevated LDL or Elevated LDL or
Low HDLLow HDL Elevated Elevated
homocysteinhomocystein SmokingSmoking Drug abuseDrug abuse
Alcohol AbuseAlcohol Abuse Oral ContraceptivesOral Contraceptives PregnancyPregnancy Migraine HeadachesMigraine Headaches ObesityObesity Sleep apneaSleep apnea Carotid stenosisCarotid stenosis
A combination of A combination of these risk factors these risk factors will increase risk of will increase risk of stroke!stroke!
Many Causes of StrokeMany Causes of Stroke
THE BURDEN OF STROKE THE BURDEN OF STROKE Anually more than 15 million people world Anually more than 15 million people world
wide suffer a stroke, 5.5 million die and 5 wide suffer a stroke, 5.5 million die and 5 million are left with permanent disability.million are left with permanent disability.
Stroke is 2nd most common cause of Stroke is 2nd most common cause of death(9.7%).death(9.7%).
Incidence of stroke is on the increase in India Incidence of stroke is on the increase in India and other developing countries.and other developing countries.
More than 80% of stroke occurs in More than 80% of stroke occurs in underdeveloped and developing countries.underdeveloped and developing countries.
Cruide annual incidence rate for first ever Cruide annual incidence rate for first ever stroke (FES) is 145 per 100,000 Persons.stroke (FES) is 145 per 100,000 Persons.
Case fatality rate at 28 days after FES was Case fatality rate at 28 days after FES was 29.8%.29.8%.Of the surviving patients 38.5% had moderate Of the surviving patients 38.5% had moderate to severe disability. Hypertension (BP>140/90 alone or to severe disability. Hypertension (BP>140/90 alone or in various combination) was present in 82.8% cases. in various combination) was present in 82.8% cases. (dalal et al, Mumbai stroke registry,2005-2006).(dalal et al, Mumbai stroke registry,2005-2006).
WHO estimated that in 1990 ,out of a total 9.4 million WHO estimated that in 1990 ,out of a total 9.4 million deaths in India , 619,000 deaths were due to stroke. deaths in India , 619,000 deaths were due to stroke. This gives stroke mortality rate of 73 per 100,000 This gives stroke mortality rate of 73 per 100,000 population. population. 1880 people die every day in India due 1880 people die every day in India due to stroketo stroke..
In 1990 the estimated no of death due to stroke were In 1990 the estimated no of death due to stroke were 22 times that due to malaria,1.4 times that due to 22 times that due to malaria,1.4 times that due to tuberculosis,4 times that due to RHD, and almost tuberculosis,4 times that due to RHD, and almost equal to IHD.equal to IHD.
Stroke mortality rate is declining in USA and other Stroke mortality rate is declining in USA and other developed countries it is likely to increase in India.developed countries it is likely to increase in India.
Stroke is a treatable Stroke is a treatable condition.condition.
IV tPA is approved for use within 3 hours ( 4.5 IV tPA is approved for use within 3 hours ( 4.5 hours) .(NINDS)hours) .(NINDS)
Intra-arterial therapy has proven to be safe Intra-arterial therapy has proven to be safe and effective within 6 hours (PROACT II) and effective within 6 hours (PROACT II)
Combined IV/IA may be more effective than IV Combined IV/IA may be more effective than IV t-PA (Interventional Management of Stroke -t-PA (Interventional Management of Stroke -IMS)IMS)
Mechanical and laser catheter technologies Mechanical and laser catheter technologies are showing great promise (Angio-Jet)are showing great promise (Angio-Jet)
Stroke: The ChallengeStroke: The Challenge
Only 1-3% of all stroke victims Only 1-3% of all stroke victims receive treatment with tPA in the receive treatment with tPA in the US . US .
25% of Acute MI patients receive 25% of Acute MI patients receive treatment (lytics or PTCA) in the US treatment (lytics or PTCA) in the US ..
Mean time to presentation Mean time to presentation AMI: 3hrsAMI: 3hrs Acute Stroke: 4-10hrs.Acute Stroke: 4-10hrs.
Reasons for lack of Reasons for lack of treatment:treatment:1.1. Patient’s inability to recognize stroke symptomsPatient’s inability to recognize stroke symptoms
40% of stroke patients can’t name a single 40% of stroke patients can’t name a single sign or symptom of stroke or stroke risk sign or symptom of stroke or stroke risk factor.factor.
75% of stroke patients misinterpret their 75% of stroke patients misinterpret their symptomssymptoms
86% of patients believe that their symptoms 86% of patients believe that their symptoms aren’t serious enough to seek urgent carearen’t serious enough to seek urgent care
2.2. Physician’s lack of experience with stroke Physician’s lack of experience with stroke treatment and therefore reluctance to “risk” treatment and therefore reluctance to “risk” treatmenttreatment
3.3. Lack of organized delivery of care in many Lack of organized delivery of care in many medical centers throughout the country.medical centers throughout the country.
Current Status of Specific Treatment Current Status of Specific Treatment for Acute Ischemic Strokefor Acute Ischemic Stroke
YesYes 1. Tissue plasminogen activator 1. Tissue plasminogen activator
within 3-4.5 hrs.within 3-4.5 hrs. 2. Aspirin within 48 hrs.2. Aspirin within 48 hrs. 3. Management in SCU3. Management in SCUMay BeMay Be 1. Neuroprotection1. NeuroprotectionNo ?No ? 1. Heparin, Heparinoids1. Heparin, Heparinoids 2. Hemodilution2. Hemodilution 3. Steroids3. Steroids
Acute Stroke Acute Stroke TreatmentsTreatments
% patients % patients that can that can benefitbenefit
Prevention Prevention death/dependency per death/dependency per
100 treated100 treated
Prevention Prevention death/dependency per death/dependency per
100 admitted100 admitted
Stroke UnitStroke Unit 90%90% 55 4.54.5
ThrombolysisThrombolysis0-3hr0-3hr
10% 10% ischaemic ischaemic
strokesstrokes1212 11
AspirinAspirin0-48hr0-48hr
65% 65% ischaemic ischaemic
strokesstrokes11 0.50.5
HemicraniectomyHemicraniectomy0-48hr0-48hr
0.5%0.5%Ischaemic Ischaemic
strokesstrokes2222 0.10.1
Slide by Prof G Ford, presented at UKCRN 21.11.2007 ,adapted from Gilligan et al 2005
Pre of hospital recognition of Pre of hospital recognition of stoke. FASTstoke. FAST
FFacial Weaknessacial Weakness Can person smile Can person smile Has mouth droppedHas mouth dropped
AArm Weaknessrm Weakness Can person raise both armsCan person raise both arms
SSpeech problemspeech problems Can person speak clearly Can person speak clearly
and understand what you sayand understand what you say
TTest all three symptomsest all three symptoms
Stroke Association Stroke Association campaign to raise campaign to raise awarenessawareness
Practice staff should be Practice staff should be trained to inform doctor trained to inform doctor immediately if patient immediately if patient calls with symptoms calls with symptoms identifiable identifiable
Ambulance crews now Ambulance crews now trained to use FAST trained to use FAST score to prioritise Calls score to prioritise Calls and dispatch.and dispatch.
Act FAST call 108 Act FAST call 108 ambulance.ambulance.
Section 1 Slide 30
Onset to Entry (By referral method)
ASIST data 1999
0
10
20
30
40
50
60
70
0-<1 1-<2 2-<3 3-<4 4-<5 5-<6 6-<9 9-<12 12-<24 >=24
Hours
Pt
Nu
mb
ers 999
GP
Other
GP+999
Pre Hospital carePre Hospital care Ambulance services ,health care Ambulance services ,health care
professionals and general public should professionals and general public should receive education concerning the importance receive education concerning the importance of early recognition of stroke, emphasing of early recognition of stroke, emphasing stroke is a medical emergency.stroke is a medical emergency.
Stroke patients should be given a high Stroke patients should be given a high priority by ambulance service.priority by ambulance service.
Ambulance services should be trained to Ambulance services should be trained to identify stroke by various tools and protocols.identify stroke by various tools and protocols.
Ambulance services should transfer Ambulance services should transfer suspected patients to hospital with stoke unit suspected patients to hospital with stoke unit care.care.
EMS response to 108 call:EMS response to 108 call:WILL QUESTION:WILL QUESTION: Time of onset of stroke symptoms.Time of onset of stroke symptoms. Determine nature of neurological symptoms Determine nature of neurological symptoms
(F.A.S.T.).(F.A.S.T.). NIH Stroke Scale or Glasgow Coma Scale NIH Stroke Scale or Glasgow Coma Scale
(language/motor response/eye movement).(language/motor response/eye movement). Hx: recent illness, surgery or trauma.Hx: recent illness, surgery or trauma. Recent use of medication/illicit drugs.Recent use of medication/illicit drugs. Notify receiving hospital that patient Notify receiving hospital that patient
appears to be an acute stroke and gives appears to be an acute stroke and gives time window.time window.
Guidelines for EMS management of Guidelines for EMS management of patients with suspected strokepatients with suspected stroke
RecommendedRecommended Manage ABCsManage ABCs Cardiac monitoringCardiac monitoring Intravenous accessIntravenous access O2(if spo2,92%)O2(if spo2,92%) Assess for Assess for
hypoglycemiahypoglycemia NBMNBM Alert receiving EDAlert receiving ED Rapid transfer to Rapid transfer to
closest stroke centreclosest stroke centre
Not recommendedNot recommended Dextrose containg Dextrose containg
fluid in non fluid in non hypoglycemic patientshypoglycemic patients
Hypotension/excessive Hypotension/excessive BP reductionBP reduction
Excess IV fluidsExcess IV fluids
Stroke units: State of the Art
Admission to a unit that is dedicated to the care of stroke patients helps to reduce mortality and morbidity.
Stroke: Differential Stroke: Differential DiagnosisDiagnosis
SyncopeSyncope Partial epileptic Partial epileptic
seizure with Todd’s seizure with Todd’s paresisparesis
Migraine attack Migraine attack (aura)(aura)
HypoglycaemiaHypoglycaemia HysteriaHysteria IntoxicationIntoxication
Subarachnoid Subarachnoid haemorrhagehaemorrhage
NeuroinfectionNeuroinfection NeoplasmNeoplasm Brain injuryBrain injury Multiple sclerosisMultiple sclerosis Peripheral vertigoPeripheral vertigo
PHYSICAL EXAMPHYSICAL EXAM
GPE,ABCs, Pulse Oximetry,temp.GPE,ABCs, Pulse Oximetry,temp. Carotid Bruits, JVP, Irregular Carotid Bruits, JVP, Irregular
RhythmRhythm Head and Neck, Chest, AbdomenHead and Neck, Chest, Abdomen Skin –Jaundice, Purpura, PetechiaSkin –Jaundice, Purpura, Petechia
Early diagnostic testsEarly diagnostic testsALL PATIENTSALL PATIENTS Non contrast brain CT Non contrast brain CT
or brain MRIor brain MRI Blood glucoseBlood glucose RFT,S. electrolytesRFT,S. electrolytes ECGECG Markers of cardiac Markers of cardiac
ischemiaischemia CBC, Plat count*CBC, Plat count* PT,INR,*APTT*PT,INR,*APTT* O2 SaturationO2 Saturation
SELECTEDSELECTED PATIENTSPATIENTS LFTLFT Toxicology screenToxicology screen Blood alcohol levelBlood alcohol level Pregnancy testPregnancy test ABGABG Chest radiographyChest radiography LP-if SAH is suspected LP-if SAH is suspected
and CT is negativeand CT is negative EEG –if seizures are EEG –if seizures are
suspected. suspected.
EARLY DIAGNOSIS: EARLY DIAGNOSIS: NON CONTRAST CT SCAN OF BRAINNON CONTRAST CT SCAN OF BRAIN
Initial imaging modality in hyper ac strokeInitial imaging modality in hyper ac stroke Widely available, quick, easy to performWidely available, quick, easy to perform Accurately identifies ICH,SAHAccurately identifies ICH,SAH EARLY SIGNS OF CEREBRAL ISCHAEMIAEARLY SIGNS OF CEREBRAL ISCHAEMIA Hyper dense MCA artery signHyper dense MCA artery sign Hyper dense dot signHyper dense dot sign Hypo density of insular ribbonHypo density of insular ribbon Hypoensity of basal gangliaHypoensity of basal ganglia loss of grey white matter differentiation in cortical ribbonloss of grey white matter differentiation in cortical ribbon sulcal effacementsulcal effacement EARLY SIGNS ARE ASSOCIATED WITH POORER EARLY SIGNS ARE ASSOCIATED WITH POORER
OUTCOMESOUTCOMES
Early HypodensityEarly Hypodensity
Hypodensity
Hyperdense middle Hyperdense middle cerebral arterycerebral artery
Hyperdense middle cerebral artery
BRAIN IMAGING (CONTD)BRAIN IMAGING (CONTD)MULTI MODEL CTMULTI MODEL CT (A) (A) Perfusion CT- more sensitive and specific to detect Perfusion CT- more sensitive and specific to detect
ischaemia.ischaemia. (b) CT Angio-for intra and extra cranial (b) CT Angio-for intra and extra cranial
vasculaturevasculatureMULTIMODEL MRIMULTIMODEL MRI T1,T2,PDT1,T2,PD DWI-Early visualization of ischaemic regions within DWI-Early visualization of ischaemic regions within
minutes of stroke.minutes of stroke. PWI,MRA,FLAIR,PWI,MRA,FLAIR,
MRI MORE SENSITIVE THAN CT(26%CT VS 83 %MRI) MRI MORE SENSITIVE THAN CT(26%CT VS 83 %MRI) FOR AC ISCHAEMIC STROKEFOR AC ISCHAEMIC STROKE
VASCULAR IMAGINGVASCULAR IMAGING TCD USG,CAROTID DUPLEX SONO,CATHETER ANGIO.TCD USG,CAROTID DUPLEX SONO,CATHETER ANGIO.
Multimodal CT ImagingMultimodal CT Imaging
Tissue Status
Bioenergetic Compromise
Perfusion Status
Hemodynamic Compromise
Vessel Status
Occlusions or Stenoses
CT PCT CTA
Acute Stroke: CT vs. MRIAcute Stroke: CT vs. MRI
Multimodal Diffusion-Multimodal Diffusion-Perfusion MRIPerfusion MRI
Tissue Status
Bioenergetic Compromise
Perfusion Status
Hemodynamic Compromise
Vessel Status
Occlusions or Stenoses
DWI PWI MRA
Arterial HypertensionArterial Hypertension Management of hypertension is Management of hypertension is
controversial.controversial.
Data are inconclusive,or conflicing.Data are inconclusive,or conflicing.
Elevations of Elevations of BP BP >160 mm of hg are >160 mm of hg are
detected in >60 % patients.detected in >60 % patients.
Many patients have spontaneous decline in Many patients have spontaneous decline in
BP during first 24 hours onset of stroke.BP during first 24 hours onset of stroke.
Both elevated and low bp are associated Both elevated and low bp are associated
with poor prognosis.with poor prognosis.
A reasonable goal is to lower BP by 15% during A reasonable goal is to lower BP by 15% during first 24 hours after onset of stroke.first 24 hours after onset of stroke.
It is generally agreed that antihypertensive It is generally agreed that antihypertensive medicines can be restricted medicines can be restricted
24 hours after the stroke, in patients who have 24 hours after the stroke, in patients who have pre existing hypertension and are neurologically pre existing hypertension and are neurologically stable. stable.
DO NOT USE SUB LINGUAL NIFEDIPINE.IT DO NOT USE SUB LINGUAL NIFEDIPINE.IT MAY BE HAZARDOUS.MAY BE HAZARDOUS.
Treatment of Arterial HypertensionTreatment of Arterial Hypertension((for patients who are not candidates for r TPA)for patients who are not candidates for r TPA)
The consensus is that antihypertensive The consensus is that antihypertensive agents should be withheld unless the agents should be withheld unless the diastolic blood pressure is >120 mm Hg diastolic blood pressure is >120 mm Hg or unless the systolic blood pressure is or unless the systolic blood pressure is >220 mm Hg (level V)>220 mm Hg (level V)
ARTERIAL HYPOTENSIONARTERIAL HYPOTENSION
SBP<100 and DBP <70 is associated with SBP<100 and DBP <70 is associated with higher mobidity and mortality.higher mobidity and mortality.
Causes of hypotension should be sought. Causes of hypotension should be sought. Potential causes are aortic dissection, Potential causes are aortic dissection, volume depletion, blood loss, decreased volume depletion, blood loss, decreased cardiac output sec to MI or cardiac cardiac output sec to MI or cardiac arrhythmia.arrhythmia.
hypovolemia should be corrected with hypovolemia should be corrected with normal saline.normal saline.
T-PA for Acute Ischemic T-PA for Acute Ischemic StrokeStroke
NEJM 95:333,1581-87NEJM 95:333,1581-87 624 patients randomized624 patients randomized 3 hour window3 hour window at three month. 30% less likely to have at three month. 30% less likely to have
minimal or no disabilityminimal or no disability 6.4% risk of hemorrhage6.4% risk of hemorrhage No change in mortality at 6 mosNo change in mortality at 6 mos
Cerebral infarct <3hrsCerebral infarct <3hrs
Onset
Infarct
Ischaemic penumbra
Cerebral infarct 6hrsCerebral infarct 6hrs
Infarct
Ischaemic penumbra
Cerebral infarct 24hrsCerebral infarct 24hrs
Infarct
Ischaemic penumbra
Intravenous thrombolysisIntravenous thrombolysis
The US FDA approved the use of r tpa in 1996 on the The US FDA approved the use of r tpa in 1996 on the basis of the results of the NINDS r TPA stroke Study.basis of the results of the NINDS r TPA stroke Study.
Patients treated with tpa were 30 % more likely to Patients treated with tpa were 30 % more likely to have minimal or no disability at 3 months compared have minimal or no disability at 3 months compared with placebo treated patients.with placebo treated patients.
Treatment with tpa resulted in 11 to 13 % absolute Treatment with tpa resulted in 11 to 13 % absolute increase in the number of patients with excellent increase in the number of patients with excellent outcomes.outcomes.
Mortality rate at 3 months was 17 % in tpa group and Mortality rate at 3 months was 17 % in tpa group and 21 % in placebo treated group.21 % in placebo treated group.
Symptomatic intracerebral haemorrhage occurred in Symptomatic intracerebral haemorrhage occurred in 6.4% of pts receiving tpa vs 0.6% of the palcebo group.6.4% of pts receiving tpa vs 0.6% of the palcebo group.
CRITERIA FOR THROMBOLYSIS CRITERIA FOR THROMBOLYSIS WITH rTPAWITH rTPA
INCLUSION CRITERIAINCLUSION CRITERIA Clinical signs and symptoms consistent with ischaenic Clinical signs and symptoms consistent with ischaenic
stroke.stroke. MEASURABLE NEUROLOGIC DEFICITMEASURABLE NEUROLOGIC DEFICIT NEUROLOGICAL SIGNS SHOULD NOT BE CLEARING NEUROLOGICAL SIGNS SHOULD NOT BE CLEARING
SPONTANEOUSLY.SPONTANEOUSLY. Neurological signs should not be minor or isolated.Neurological signs should not be minor or isolated. Onset of symptoms <3 hour before beginning treatmentOnset of symptoms <3 hour before beginning treatment Caution should be exercised in treating a patient with a Caution should be exercised in treating a patient with a
major deficit.major deficit. Symptoms of stroke should not be s/o SAH.Symptoms of stroke should not be s/o SAH. No head trauma or prior stroke in previous 3 months.No head trauma or prior stroke in previous 3 months. No MI in previous 3 months.No MI in previous 3 months. No GI OR urinary tract haemorrhage in previous 21 days. No GI OR urinary tract haemorrhage in previous 21 days.
Cont..Cont.. No major surgery in previous 14 days.No major surgery in previous 14 days. No arterial puncture at a noncompressible site in previous 7 No arterial puncture at a noncompressible site in previous 7
days.days. NO H/O previous intra cranial haemorrhage.NO H/O previous intra cranial haemorrhage. Systolic BP<185 and diastolic <110Systolic BP<185 and diastolic <110 No evidence of active bleeding or ac trauma on examnNo evidence of active bleeding or ac trauma on examn Not taking oral anticoagulant or if being taken INR <1.7Not taking oral anticoagulant or if being taken INR <1.7 If receiving HEPARIN in previous 48 hours A PTT must be If receiving HEPARIN in previous 48 hours A PTT must be
normal range.normal range. Platelet count <1 lac mm3Platelet count <1 lac mm3 Blood glucose >50 mg %Blood glucose >50 mg % No seizure with postictal residual neurol impairements.No seizure with postictal residual neurol impairements. CT does not show a multilobar infarction (hypodensity >1/3 CT does not show a multilobar infarction (hypodensity >1/3
cerebral hemisphere)cerebral hemisphere) The patient or family understands the potential risks and The patient or family understands the potential risks and
benefits of treatment.benefits of treatment.
NINDS tPA Stroke TrialNINDS tPA Stroke Trial
0
10
20
30
0
10
20
30
tPA tPAPlacebo Placebo
31
20 9
8
20
1
NIHSS Excellent Recovery (%)
Total Death Rate (%)
Hemorrhagep < .05
New England Journal, 1995
IV administration of tpa.IV administration of tpa.
Infuse 0.9mg/kg(max 90 mg ) over 60 mnts Infuse 0.9mg/kg(max 90 mg ) over 60 mnts with 10 % of the dose given as bolus over 1 with 10 % of the dose given as bolus over 1 mnt.mnt.
Admit pt in neuro ICU or stroke unit.Admit pt in neuro ICU or stroke unit. Perform neurological assessment every 15 Perform neurological assessment every 15
mnts during the infusion and every 30 mnts mnts during the infusion and every 30 mnts thereafter for next 6 hours then hourly until thereafter for next 6 hours then hourly until 24 hours after treatment.24 hours after treatment.
If pt develop severe head ache,ac HTN, If pt develop severe head ache,ac HTN, nausea,or vomitting discontinue infusion and nausea,or vomitting discontinue infusion and obtain emergency CT scan.obtain emergency CT scan.
Besides bleeding complications r tpa have potential Besides bleeding complications r tpa have potential
side effect of angioedema that may cause partial air side effect of angioedema that may cause partial air
way obstruction.way obstruction.
A patient with seizure at the time of onset of stroke A patient with seizure at the time of onset of stroke
may be eligible for tpa if physician is convinced that may be eligible for tpa if physician is convinced that
residual impairements are secondary to stroke not a residual impairements are secondary to stroke not a
postictal phenomenon.postictal phenomenon.
IV streptokinase is not recommended .IV streptokinase is not recommended .
IV ancrod, IV ancrod,
tenecteplase,reteplase,desmoteplase,urokinase outside tenecteplase,reteplase,desmoteplase,urokinase outside
the setting of clinical trial is not recommendedthe setting of clinical trial is not recommended
Time is BrainTime is Brain““The typical patient loses 1.9 million neurons The typical patient loses 1.9 million neurons
each minute in which stroke is untreated”each minute in which stroke is untreated”
Symptom-to-needle time in minutes
Odd
s R
atio
(c
orre
cted
; 95%
CI)
fa
vour
able
Out
com
e
60 90 120 150 180 210 240 270 300 330 360
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
NNT:3.5*
NNT:7*
(11)**
NNT:9*
(13)**
NNT:11*
(>30)**
Upper 95% CI
Mean
Lower 95% CI
* NNT at absolute point of time ** NNT for each 90 min interval
Symptom-to-needle time in minutes
Odd
s R
atio
(c
orre
cted
; 95%
CI)
fa
vour
able
Out
com
e
60 90 120 150 180 210 240 270 300 330 360
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
NNT:3.5*
NNT:7*
(11)**
NNT:9*
(13)**
NNT:11*
(>30)**
Upper 95% CI
Mean
Lower 95% CI
* NNT at absolute point of time ** NNT for each 90 min interval
Slide by Prof G Ford, presented at UKCRN 21.11.2007 based on Saver, Stroke 2006
Time is brain: benefit from rt-PA declines with increasing delay from onset to treatment time
Benefit
Harm
3 hours 6 hours
Upper and lower 95% confidence limits
Line of no effect
IST-3 protocol
Thrombolysis in EuropeThrombolysis in Europe
0
10
20
30
40
50
60
rt-P
A f
or
str
ok
e p
er
millio
n p
op
'n
Finland
Austria
SwedenNorway
Belgium
Spain
GermanyNetherlands
Denmark
Italy
UK
GreeceFrance
Portugal
Slide donated by P. Sandercock, IST-3 trialists meeting, Brussels 2006
Intra arterial ThrombolysisIntra arterial Thrombolysis PROACT IIPROACT II
Intra arterial ProurokinaseIntra arterial Prourokinase 6 Hour time window6 Hour time window Relative risk reduction of 15% in functional Relative risk reduction of 15% in functional
outcomeoutcome No difference in mortalityNo difference in mortality Procedural complication 9%Procedural complication 9% Early Intra cerebral haemorrhage 10%Early Intra cerebral haemorrhage 10% INTRA ARTERIAL THROMBOLYS IS REASONABLE INTRA ARTERIAL THROMBOLYS IS REASONABLE
IN PATIENTS WHO HAVE C/I TO USE OF IV TPA IN PATIENTS WHO HAVE C/I TO USE OF IV TPA LIKE RECENT SURGERY.LIKE RECENT SURGERY.
Guidelines for Guidelines for Anticoagulant TherapyAnticoagulant Therapy
Urgent administration of anticoagulants has not Urgent administration of anticoagulants has not yet been associated with lessening the risk of yet been associated with lessening the risk of early recurrent stroke or improving outcomes. early recurrent stroke or improving outcomes. Because it can increase the risk of brain Because it can increase the risk of brain hemorrhage, routine use cannot be hemorrhage, routine use cannot be recommended.recommended.
American Heart Association, 2003
Guidelines for Guidelines for Anticoagulant TherapyAnticoagulant Therapy
Anticoagulants are Anticoagulants are notnot recommended recommended for any subgroup of patients with acute for any subgroup of patients with acute stroke based on any presumed stroke based on any presumed mechanism or location (e.g., mechanism or location (e.g., cardioembolic, large vessel cardioembolic, large vessel atherosclerotic, vertebrobasilar, or atherosclerotic, vertebrobasilar, or “progressing” stroke) because data are “progressing” stroke) because data are insufficient.insufficient.American Academy of Neurology / AHA, 2003
Acute Treatment with Acute Treatment with Antiplatelet AgentsAntiplatelet Agents Aspirin (initial dose is 325 mg) should be given within 24 Aspirin (initial dose is 325 mg) should be given within 24
to 48 hours of stroke onset in most patients (Class 1, level to 48 hours of stroke onset in most patients (Class 1, level A). A).
The administration of aspirin as an adjunctive therapy, The administration of aspirin as an adjunctive therapy, within 24 hours of the use of thrombolytic agents, is not within 24 hours of the use of thrombolytic agents, is not recommended (Class 3,level A). recommended (Class 3,level A).
Aspirin should not be used as a substitute for other acute Aspirin should not be used as a substitute for other acute interventions, especially intravenous administration of interventions, especially intravenous administration of rtPA, for the treatment of acute ischemic stroke (Class rtPA, for the treatment of acute ischemic stroke (Class 3,level B).3,level B).
No recommendation can be made about the urgent No recommendation can be made about the urgent administration of other antiplatelet aggregating agents administration of other antiplatelet aggregating agents alone or in combination with aspirin (Class 3,level C).alone or in combination with aspirin (Class 3,level C).
Outside the setting of clinical trials IV administration of Outside the setting of clinical trials IV administration of antiplatelet agents that inhibit the glycoprotein 2b/3a ptor antiplatelet agents that inhibit the glycoprotein 2b/3a ptor is not recommended.(Class 3,level B).is not recommended.(Class 3,level B).
Benefit of Early Aspirin Treatment Benefit of Early Aspirin Treatment in Acute Ischemic Strokein Acute Ischemic Stroke
496636
205 168
12311327
16621843
0
500
1000
1500
2000
RecurrentIschemic Stroke
HemorrhagicStroke
Death Death or NonfatalStroke
Aspirin, n=20,207 Control, n=20,190
9 patients benefit per 1000 treated (p<0.001)
Combined Data from IST, CAST, MAST-I
Hemodilution,Vasodialators,anHemodilution,Vasodialators,and induced hypertensiond induced hypertension
Hemodilution with or without venesection Hemodilution with or without venesection and volume expansion is not and volume expansion is not recommended for treatment of ac recommended for treatment of ac ischaemic stroke.(Class 3,level A)ischaemic stroke.(Class 3,level A)
Vasodialators like pentoxifyline is not Vasodialators like pentoxifyline is not recommended for treatment of ac stroke.recommended for treatment of ac stroke.(Class 3 ,level A)(Class 3 ,level A)
Drug induced hypertension outside the Drug induced hypertension outside the setting of clinical trials is not setting of clinical trials is not recommended .)recommended .)
MERCI TRIALMERCI TRIAL
Anterior circ strokes onlyAnterior circ strokes only Treatment <8 hoursTreatment <8 hours 151 patients entered151 patients entered
MERCI RESULTSMERCI RESULTS
Recanalization in 46%Recanalization in 46% Historical 18%Historical 18%
Complication rate 7% (SAH, device Complication rate 7% (SAH, device fx, embolization)fx, embolization)
With recanalization, good outcome With recanalization, good outcome (46% vs. 10%) and mortality (46% vs. 10%) and mortality improved (32% vs. 54%)improved (32% vs. 54%)
ICH rate 7.8%ICH rate 7.8%
Thrombolysis AugmentationThrombolysis Augmentation
UltrasoundUltrasound With or without micro-bubblesWith or without micro-bubbles
Micro-bubbles containing TPAMicro-bubbles containing TPA
Combination with G2B3A inhibitorsCombination with G2B3A inhibitors
Neuroprotective agentsNeuroprotective agents
At present no neuroprotective agent At present no neuroprotective agent is found to be effective in improving is found to be effective in improving outcomes after stroke,and therefore outcomes after stroke,and therefore none currently can be none currently can be recommended(class 3,level A)recommended(class 3,level A)
General Ac treatment after General Ac treatment after HospitalizationHospitalization 25 %of patients may have neurological 25 %of patients may have neurological
worsening during first 24-48 hours.worsening during first 24-48 hours. The use of stroke unit is recommended to The use of stroke unit is recommended to
improve general management.improve general management. Early mobilization of less severely affected Early mobilization of less severely affected
patients is recommended.patients is recommended. Assessment of swallowing before staring Assessment of swallowing before staring
eating or drinking is recommended.eating or drinking is recommended. Patients with suspected pneumonia,UTI should Patients with suspected pneumonia,UTI should
be treated with antibiotics.be treated with antibiotics.
Sub cut anticoagulants are recommended for Sub cut anticoagulants are recommended for treatment of immobilized patients to prevent treatment of immobilized patients to prevent DVT.Ideal timing for starting these medications DVT.Ideal timing for starting these medications is not known.is not known.
The use of intermittent external compression The use of intermittent external compression devices is recommended for treatment of devices is recommended for treatment of patients who can not receive antcoagulants.patients who can not receive antcoagulants.(Class 2a ,level B)(Class 2a ,level B)
Pulmonary embolism accounts for 10% of Pulmonary embolism accounts for 10% of deaths after stroke,and complicaton may be deaths after stroke,and complicaton may be detected in 1%of patients who have had a detected in 1%of patients who have had a stroke.stroke.
Patients who cannot take food and fluids Patients who cannot take food and fluids orally should receive orally should receive nasogastric,nasodudenal or PEG feedings to nasogastric,nasodudenal or PEG feedings to maintain hydration and nutrition.The timing maintain hydration and nutrition.The timing of PEG is uncertain.of PEG is uncertain.
Nutritional supplements are not needed.Nutritional supplements are not needed. Prophylactic administration antibiotic is not Prophylactic administration antibiotic is not
recommended.recommended. If possible the placement of indwelling If possible the placement of indwelling
bladder catheters should be avoided because bladder catheters should be avoided because of associated risk of UTI.(class3 ,level C)of associated risk of UTI.(class3 ,level C)
Treatment of ac neurological Treatment of ac neurological ComplicationsComplications
Brain EdemaBrain Edema
Development of brain edema is gradual and occurs most Development of brain edema is gradual and occurs most frequently 3- 5 days after stroke.frequently 3- 5 days after stroke.
Brain edema is most frequent neurological cause of death in Brain edema is most frequent neurological cause of death in patients with stroke.patients with stroke.
Early CTscan hypodensity,defined as <12 hours after Early CTscan hypodensity,defined as <12 hours after onset ,of >50 %of the MCA territory and presence of onset ,of >50 %of the MCA territory and presence of hyperdense MCA signs are independent predictors of hyperdense MCA signs are independent predictors of neurological deterioration.neurological deterioration.
Large hypodensity>2/3 of MCA terrority on CT and large Large hypodensity>2/3 of MCA terrority on CT and large hypoperfusion on CT perfusion maps predicted hypoperfusion on CT perfusion maps predicted development of malignant MCA infarct.development of malignant MCA infarct.
Modest fluid restrictionModest fluid restriction Avoidence of hypo osmolar fluids like Avoidence of hypo osmolar fluids like
GDW.GDW. Control of fever,hypoxia,hypercapnia.Control of fever,hypoxia,hypercapnia. Elevation of head end of bed by 30 Elevation of head end of bed by 30
degree.degree. Hyperventilation to a partial co2 Hyperventilation to a partial co2
pressure of 28-30 mm of hg.pressure of 28-30 mm of hg.
Management of brain edema and increased ICP
Administration of mannitol 0.25-Administration of mannitol 0.25-0.50gm /kg IV over 30 mnts every 6 0.50gm /kg IV over 30 mnts every 6 hours.hours.
Diuresis(furosemide 40 mg IV).Diuresis(furosemide 40 mg IV). Drainage of CSF.Drainage of CSF. Resection of infarcted Resection of infarcted
tissue./decompressive surgery.tissue./decompressive surgery. Antihypertensive agents particularly Antihypertensive agents particularly
those causing cerebral vasodilation those causing cerebral vasodilation should be avoided.should be avoided.
Contd……Contd…… Patients with ac hydrocephalus in ischaemic stroke most Patients with ac hydrocephalus in ischaemic stroke most
commonly affecting cerebellum can be treated with commonly affecting cerebellum can be treated with placement of a ventricular drain.(class 1 level B)placement of a ventricular drain.(class 1 level B)
Decompressive craniectomy is indicated for treatment of Decompressive craniectomy is indicated for treatment of large cerebellar infarcts in patients with clinical large cerebellar infarcts in patients with clinical deterioration and evidence of early brain stem deterioration and evidence of early brain stem compression or hydrocephalus.This is potentially life compression or hydrocephalus.This is potentially life saving measure and clinical recovery may be very good.saving measure and clinical recovery may be very good.(class 1 ,level B)(class 1 ,level B)
Decompressive surgery for malignant brain edema may Decompressive surgery for malignant brain edema may be life saving in selected patients with complete MCA be life saving in selected patients with complete MCA infarction who are significant risk for developing trans infarction who are significant risk for developing trans tentorial herniation.Timing of surgery is poorly tentorial herniation.Timing of surgery is poorly defined,with some opting for early surgery (in 24 hours)defined,with some opting for early surgery (in 24 hours)
Suboccipital craniotomy is the treatment to relieve both Suboccipital craniotomy is the treatment to relieve both hydrocephalus and brain stem compression caused by hydrocephalus and brain stem compression caused by large cerebellar infarctions.large cerebellar infarctions.
No specific recommendation is made for No specific recommendation is made for treatment of patients with asymptomatic treatment of patients with asymptomatic haemorrhagic transformation after haemorrhagic transformation after ischaemic stroke.ischaemic stroke.
Corticosteroids are not recommended for Corticosteroids are not recommended for treatment of cerebral edema and treatment of cerebral edema and increased ICP(class 3,level A)increased ICP(class 3,level A)
Prophylactic administration of Prophylactic administration of anticonvulsants in patients of stroke who anticonvulsants in patients of stroke who have not had seizures is not have not had seizures is not recommended(class 3 ,level C)recommended(class 3 ,level C)
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