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THROMBOLYSIS IN ACUTE STROKE

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DOSE

IV Alteplase (0.9 mg/kg, maximum dose 90 mg over 60 min with initial 10% of dose given as bolus over 1 min)

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ALTEPLEASE CAN BE GIVEN IN FOLLOWING CONDITIONS

  • Age > 90yrs
  • Diabetes
  • Single or dual antiplatelet
  • End stage renal disease
  • severe hepatic dysfunction
  • Early improvement in symptoms
  • Seizure at onset 
  • History of warfarin use and an INR ≤1.7 or a PT <15 sec

  • Prior hypersensitivity

  • Recent myocardial infarction (within 3 months)

  • High likelihood of left heart thrombus (e.g.: Mitral stenosis with atrial fibrillation)

  • Diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions (COR2A)

  • Pregnancy (COR2B)

  • Lactating woman

  • Menstruation (COR2A)

  • Major surgery <14days (COR2B)

  • Major trauma <14days (COR2B)

  • GI and genitourinary bleeding <21 days (COR2B)

  • Extracranial cervical dissections (COR2A)

  • Intracranial arterial dissection (COR2B)

  • Unruptured intracranial aneurysm (moderate size <10mm) (COR2A)

  • Unruptured giant intracranial aneurysm (COR2B)

  • Cerebral microbleeds (<10) (COR2A)

  • Cerebral microbleeds (.10) (COR2B)

  • Extra-axial intracranial neoplasms (COR2A)

  • Acute STEMI  (COR2A)

  • Recent STEMI (the right or inferior myocardium)  (COR2A)

  • Recent STEMI (left anterior myocardium) (COR2B)

  • Acute pericarditis (COR2B)

  • Left atrial or ventricular thrombus (COR2B)

  • Procedural stroke (CAG or cerebral angiography) (COR2A)

  • Systemic malignancy  (COR2B)

  • Sickle cell disease (COR2A)​

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CONTRAINDICATIONS

  • Mild non disabling stroke (COR3)

  • Full treatment dose of LMWH within the previous 24 (COR3)

  • Platelets <100 000/mm3, INR >1.7, aPTT >40 s, or PT >15 sec (COR3)

  • History of intracranial hemorrhage (COR3)

  • Intracranial/intraspinal surgery within 3 months (COR3)

  • Acute head trauma (COR3)

  • Severe head trauma within 3 m (COR3)

  • Subarachnoid hemorrhage (COR3)

  • Thrombin inhibitors or factor Xa inhibitors (COR3)

  • Infective endocarditis (can cause IC bleed) (COR3)

  • Aortic arch dissection (COR3)

  • Intra-axial intracranial neoplasm (COR3)

  • Structural GI malignancy or recent bleeding event within 21 d (COR3)

<4.5HRS
4.5-6HRS
6-24HRS
BLOOD PRESSURE
ANTIPLATELET
SURGERY
RIASED ICT
ANTICOAGULATION
CAROTID

WAKE UP STROKE

  • AIS who awake with stroke symptoms or have unclear time of onset >4.5 h from last known well or at baseline state and who have a DW-MRI lesion smaller than one- third of the MCA territory and no visible signal change on FLAIR. (COR 2A)


ASPECT 6 > 1/3 MCA : 10% POSSIBILITY

ASPECT 7 > 1/3 MCA: 1% POSSIBILITY

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MECHANICAL THROMBECTOMY

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  • 4.5-6 hrs
    Patients should receive mechanical thrombectomy with a stent retriever if they meet all the following criteria: (1) prestroke mRS score of 0 to 1; (2) causative occlusion of the internal carotid artery or MCA segment 1 (M1); (3) age ≥18 years; (4) NIHSS score of ≥6; (5) ASPECTS of ≥6; and (6) treatment can be initiated (groin puncture) within 6 hours of symptom onset. (COR 1)

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  • Although the benefits are uncertain, the use of mechanical thrombectomy with stent retrievers may be reasonable for carefully selected patients with AIS in whom treatment can be initiated (groin puncture) within 6 hours of symptom onset and who have causative occlusion of the MCA segment 2 (M2) or MCA segment 3 (M3) portion of the MCAs. (COR2B)

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  • Although its benefits are uncertain, the use of mechanical thrombectomy with stent retrievers may be reasonable for patients with AIS in whom treatment can be initiated (groin puncture) within 6 hours of symptom onset and who have prestroke mRS score >1, ASPECTS <6, or NIHSS score <6, and causative occlusion of the internal carotid artery (ICA) or proximal MCA (M1). (COR2B)

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  • Although the benefits are uncertain, the use of mechanical thrombectomy with stent retrievers may be reasonable for carefully selected patients with AIS in whom treatment can be initiated (groin puncture) within 6 hours of symptom onset and who have causative occlusion of the anterior cerebral arteries, vertebral arteries, basilar artery, or posterior cerebral arteries. (COR2B)

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6 to 24 hours

  • In selected patients with AIS within 6 to 16 hours of last known normal who have LVO in the anterior circulation and meet other DAWN or DEFUSE 3 eligibility criteria, mechanical thrombectomy is recommended. (COR 1)

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  • In selected patients with AIS within 16 to 24 hours of last known normal who have LVO in the anterior circulation and meet other DAWN eligibility criteria, mechanical thrombectomy is reasonable.(COR 2B)

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6-24HRS

DAWN

Age >80

NIHSS>10

DWI vol <20

Age <80

NIHSS>10

DWI vol < 30

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NIHSS>20

DWI vol<50

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DWI vol = a x b x c / 2

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6-16HRS

DEFUSE3

DWI vol <70

Penumbra/ DWI  volume > 1.8

RAPID SOFTWARE

Infarct CBF <30%

Penumbra T-max > 6sec

TICI SCORE:

2c : 50-99% reperfusion

3   : 100% reperfusion

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MECHANICAL THROMBECTOMY  ON ANTICOAGULATION/ THROMBOCYTOPENIA

Can undergo mechanical  thrombectomy

Platelet count >40000 can undergo mechanical thrombectomy

ACUTE MANAGEMENT OF STROKE  (BP)​

  • In acute ischemic stroke, parenteral antihypertensive medication should be recommended only if there is a hypertensive emergency with one or more of the following serious concomitant medical issues:

    • Hypertensive encephalopathy

    • Malignant Hypertension

    • Hypertensive cardiac failure/myocardial infarction

    • Aortic dissection

    • Pre-eclampsia/eclampsia

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  • Antihypertensive medication should be withheld in ischemic stroke patients unless systolic blood pressure/diastolic blood pressure(SBP/DBP) >220/120 mmHg or the mean arterial blood pressure (MAP) is >120mmHg. Lowering by 15% during the first 24 hours is recommended.

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BP MANAGEMT PRE-THROMBOLYSIS

  • If BP is >185/110 mm of Hg, Inj. labetolol 10-20mg I.V. should be given over 1-2min and may be repeated every 10 min to a maximum dose of 300mg or labetolol infusion can be started at 1-8mg/min.

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  • If labetolol is not available, nitroglycerin infusion at 5μg/min or nicardipine infusion at 5mg/hour is an alternative to labetolol.

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  • Nitroglycerin dose may be increased by 5 μg/min every 3–5 minutes to a maximum rate of 200 μg/min. Nicardipine can be increased by 2.5mg/hour every 5min up to a maximum dose of 30 mg/hour. Aim is to continue treatment till target BP <185/110 mm Hg is achieved.

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BP DURING THROMBOLYSIS

  • BP should be monitored every 15 min for 2 hours, then every 30min for next 6 hours and finally every hour for next 16 hours.  BP goal is <180/105 mmHg.

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BP MANAGEMENT IN IC BLEED

  • If systolic blood pressure is >200 mmHg or MAP is >150 mmHg (recorded twice, two or more minutes apart), then blood pressure should be aggressively treated with parenteral antihypertensive (e.g. labetolol, nitroglycerin or nicardipine or sodium nitroprusside).

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  • If systolic blood pressure is >180 mmHg or MAP is >130 mmHg (up to 150 mm Hg), use of rapidly acting oral or parenteral medication or nitroglycerin patch is advised.

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  • Target SBP should be 140mmHg – 150mmHg for at least 7 days

ANTIPLATELET  THERAPY STROKE

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Minor Stroke

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  • TIA or minor stroke (NIHSS <=3) start dual platelets, Aspirin 150-300mg and Clopidogrel (300mg loading followed by 75mg/day). Continue dual antiplatelet for 3 weeks.

  • The dose of Aspirin can be from 75 to 300mg/day. Commonly used 

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Symptomatic intracranial atherosclerosis

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  • Symptomatic intracranial atherosclerosis (70-99%) start dual platelets, Aspirin 150-300mg and Clopidogrel (300mg loading followed by 75mg/day) for 3 months.  No specific indication for 50-70% stenosis.

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  • The SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) showed no benefit of adding Wingspan stenting to aggressive medical therapy. The medical treatment–only group in SAMMPRIS had an almost 2-fold lower risk of any stroke or death within 30 days or ischemic stroke in the territory of the qualifying artery after 30 days.

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  • The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial showed that aspirin was safer and equally as effective as warfarin over a mean duration of 1.8 years.

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  • The CLAIR study showed that the combination of aspirin and clopidogrel initiated within 7 days of symptom onset for a total of 7 days was superior to aspirin alone for reducing microembolic signals on transcranial Doppler (TCD) in patients with intracranial stenosis

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Dual Antiplatelet Therapy Beyond 90 days in Symptomatic Intracranial Stenosis [LINK] The results are below:

  • Only patients with CAD and peripheral vascular disease were permitted to take clopidogrel beyond 90 days in SAMMPRIS

  • Dual vs single antiplatelet

    • Stroke risk (6% versus 10.8%)

    • Bleeding risk (4.0% on group vs 2.5% off group)

  • Half of US stroke neurologists and interventionists who responded to a survey conducted after the SAMMPRIS results were published reported that they recommended indefinite use of dual antiplatelet therapy in patients with ICAS

 

Thrombocytopenia

  • Aspirin can be given if platelet count is >50000

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RAISED ICP MANAGEMENT​

  • Initial care includes mild restriction of fluids, elevation of head end of the bed by 30 degrees and correction of factors that might exacerbate increased ICP (e.g. hypoxia, hypercarbia and hyperthermia).

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  • Hyperventilation acts immediately (reduction of the pCO2 by 5 to 10 mmHg lowers ICP by 25% to 30%) and may be used as a temporary measure to lower ICP but should be followed by another intervention to control brain edema and ICP. Hyperventilation can cause vasoconstriction that might aggravate ischemia.

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  • An intravenous bolus of 40 mg furosemide may be used in patients whose condition is rapidly deteriorating. If required, furosemide20 mg (once daily) may be continued for the first week. 3% hypertonic saline or acetazolamide 250 mg (BD) may be added in those not responding to other treatment methods.

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  • Strict intake-output chart must be maintained to avoid dehydration.

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  • In those with altered consciousness, mannitol (0.5 gm/kg intravenously given over 20 minutes) can be given every 6 to 8 hours. If clinically indicated, dose frequency may be increased to every 4 hours only if the central venous monitoring is possible. Central venous pressure should be kept between 5 and 12 mm Hg to prevent hypovolemia.This may be continued for three to five days.

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ANTICOAGULATION

  • Combination of antiplatelet and anticoagulation is not recommended, except in cases of acute coronary syndrome or stent placement.

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  • Anticoagulation should be considered for all patients who have ischemic stroke associated with mitral valve disease, prosthetic heart valves, or within 3 months of myocardial infarction.

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  • For patients with rheumatic valvular heart disease developing stroke / TIA while on VKA,an antiplatelet drug can be added.

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  • Mechanical aortic/mitral valve with history of ischemic stroke/TIA prior to its insertion, VKA therapy with target INR of 2.5 and 3.0 respectively, is recommended.

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  • Addition of aspirin along with VKA is recommended in those patients who are at low risk of bleeding.

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  • Anticoagulation should not be started until brain imaging has excluded haemorrhage, and 7 to 14 days have passed from the onset of a disabling ischemic stroke (except when a demonstrable intracardiac thrombus is present).

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  • For effective anticoagulation target, INR is 2.5 (range 2.0 to 3.0) except for mechanical cardiac valves (3.0: range 2.5 to 3.5).

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  • Warfarin and not DOAC is recommended in APLA induced thrombosis and moderate to severe MS.

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TIA  Day1

Minor stroke Day3

Moderate stroke Day6

Large stroke Day 12

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Large cerebral infarction:

  • NIHSS>15

  • Lesions involving complete arterial territory 

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MYOCARDIAL INFARCTION  

  • VKA is recommended with target INR of 2-3 for three months in acute anterior STEMI with apical akinesis or dyskinesis but with no mural thrombus.

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  • In case of presence of LA/LV mural thrombus, VKA therapy is recommended for 3 months. Patients should also be under care of a cardiologist

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  • In case of presence of mural thrombus or EF <40%, and those intolerant to VKA; LMWH, dabigatran, apixaban or rivaroxaban should be used as alternatives for 3 months.

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CARDIOEMBOLIC STROKE

  • Patients with disabling ischemic stroke (i.e. large infarction) who are in atrial fibrillation should be treated with aspirin 150 mg for the first one to two weeks before starting anticoagulation.

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  • In patients with prosthetic valves who have disabling cerebral infarction and who are at significant risk of hemorrhagic transformation, anticoagulation treatment should be stopped for one week and aspirin 150 mg should be substituted.

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  • Heparin may be started within 48 hours of cardioembolic stroke except in large infarctions. However, evidence to support this is lacking.

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  • In patients with suspected embolic stroke of undetermined source (ESUS), 24-48 hour Holter monitoring is indicated.

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ICH  RELATED TO ANTICOAGULATION/ THROMBOLYSIS

  • ICH related to acenocoumarol/warfarin should be managed with vitamin K, fresh frozen plasma (FFP) and wherever available prothrombin complex concentrate (PCC).

    • Vitamin K (10 mg IV) should be used but with FFP/PCC. Vit K alone takes at least 6 hours to normalize the INR​

    • FFP (15 to 20 ml/kg) is an effective way of correcting INR, but there is risk of volume overload and heart failure. Both PCC and factor IX complex concentrate require smaller volumes of infusion than FFP (and correct the coagulopathy faster but with greater risk of thromboembolism).

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  • Symptomatic haemorrhage after thrombolysis, administration of IV alteplase should be stopped if still infusing until NCCT head has been done. (If CT shows no evidence of bleeding, then infusion can be resumed).​​

    • If the CT shows hemorrhage, then immediately check values of: CBC, PT, a-PTT, platelets, fibrinogen and D-dimer. If fibrinogen is <100 mg/dL, then give cryoprecipitate 0.15 units/kg rounded to the nearest integer. Give 4 units of platelet rich plasma if platelet dysfunction is suspected.

    • If heparin has been administered in the past 3 hours, then follow the above paragraph on ICH related to heparin use.

    • Serious extracranial hemorrhage should be treated in a similar manner. In addition, compressible sites of bleeding should be manually compressed.

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RESTARTING VKA

  • Patients with a very high risk of thromboembolism (those with mechanical prosthetic heart valves), vitamin K antagonist therapy may be restarted at 7 to 10 days after onset of the index intracranial hemorrhage. Those with lower risk may be restarted on antiplatelet therapy.

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DABIGATRAN

Overall, Dabigatran 110 mg BID was non-inferior to warfarin but had lower rates of major bleeding episodes and Dabigatran 150 mg BID was superior to warfarin but had similar rates of major bleeding episodes

 

CrCl 30–49 ml/min with high risk of bleeding consider 110 mg twice daily

CrCl 15–30 ml/min consider 75 mg twice daily

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APPT: At trough: >2XULN Suggest excess bleeding risk

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APIXABAN

Dose 5mg BID

2.5 mg BID if (any two of)

Age ≥80 years

Body weight <60 kg

Serum creatinine level ≥1.5 mg/dl

APPT: Not useful

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RIVAROXABAN

Dose 20mg OD

15 mg OD in CrCl- 30 to 49 ml/min

APPT: Not useful

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NOTES

  • Clinicians might offer Apixaban to patients with NVAF and GI bleeding risk who require anticoagulant medication

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  • Clinicians should offer Dabigatran, Rivaroxaban, or Apixaban to patients unwilling or unable to submit to frequent periodic testing of INR levels
     

  • NOACs (Dabigatran, Rivaroxaban, and Apixaban) are not recommended in patients with severe renal impairment (CrCl <30 ml/min)

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ASPIRIN AFTER IC BLEED

Aspirin can be started after 7-30 days of IC bleed

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HAEMORRHAGIC STROKE  ON VKA

Vitamin K 10mg IV

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ICH ON DABIGATRAN/ APIXABAN/ RIVOROXABAN

CHARCOAL (DOSE < 2 HRS)

HAEMODIALYSIS FOR DABIGATRAN

rFACTOR 7A

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HEPARIN BLEED

Protamine sulphate

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DVT PROPHYLAXIS IN ICH

Pneumatic compression (1A evidence)

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CAROTID INTERVENTION

  • Patients with TIA or non-disabling stroke and ipsilateral 70-99% internal carotid artery stenosis (measured by two concordant non-invasive imaging modalities or on a catheter angiogram) should be offered carotid intervention (see below) within two weeks of the incident event unless contraindicated.

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  • Carotid intervention is recommended for selected patients with moderate (50-69%) stenosis in symptomatic patients.

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  • Carotid intervention is not recommended for patients with mild (<50%) stenosis.

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  • For older (>70 years) patients, CEA is a preferred option while younger patients CAS and CEA are found to be equivalent.

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SURGERY IN ACUTE STROKE (INFARCT)

Patients with middle cerebral artery territory infarction should be considered for decompressive hemicraniectomy and operated as early as possible, preferably within 48 hours who meet the criteria below [decision to be individualized]

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  • Decrease in the level of consciousness GCS score (total between 6 and 13, eye-motor score<9, motor score 5 or less), AND

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  • CT scan showing signs of an infarct of at least 50% of the MCA territory, with evidence of midline shift >4 mm with or without infraction in the territory of anterior or posterior cerebral artery on the same side or diffusion-weighted MRI showing infarct volume >145cm3.

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  • Patients with large cerebellar infarct causing compression of brainstem and altered consciousness should be surgically managed with suboccipital craniectomy.

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  • Symptomatic hydrocephalus should be treated surgically with cerebrospinal fluid (CSF) diversion procedure.

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SURGERY IN IC BLEED

  • Patients with cerebellar hemorrhage (>3 cm in diameter) who are deteriorating neurologically or who have signs of brain stem dysfunction should have suboccipital craniectomy and surgical evacuation of hematoma.

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  • Patients with supratentorial ICH causing midline shift and/or herniation with impairment of consciousness or deteriorating neurologically should have surgical evacuation of hematoma within 72 hours of onset of symptoms, unless they were dependent on others for activities of daily living prior to the event or their GCS is <6 (unless this is because of hydrocephalus).

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  • Patients with hydrocephalus who are symptomatic from ventricular obstruction should undergo CSF drainage procedure.

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ELECTIVE SURGERY AFTER STROKE

  • There is no specific guideline for this but should wait for 3 months for an elective surgery as brain autoregulation after large stroke could be abnormal for 3 months.

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