Ischemic%20stroke Treatment

• Elevated blood pressure is a major risk factor for both 1st and subsequent stroke
• Both elevated and low blood pressures are associated with poor outcome in acute ischemic stroke
• Mild and moderately elevated blood pressure should not be routinely lowered in the acute phase of stroke as this may worsen outcome
  
  • Avoid aggressive blood pressure lowering as this is detrimental in acute stroke

• Hypotension and hypovolemia should be corrected in order to maintain systemic perfusion levels that are essential to organ function 
• Elevated blood pressure in stroke may be due to stress of cerebrovascular event, full bladder, nausea, pain, preexisting hypertension, physiological response to increased intracranial pressure or to hypoxia
• Elevated blood pressure usually resolves spontaneously within the 1st few days after a stroke
• Excessively high blood pressure is lowered to decrease brain edema formation, reduce risk of hemorrhagic transformation of the infarct, prevent further vascular damage and preclude early recurrent stroke

• No certain benefits are indicated once antihypertensive medications in patients with SBP ≥220 mmHg or DBP ≥120 mmHg or MAP >130 are withheld or re-initiated within 48-72 hours
• Starting or restarting antihypertensive medications during hospitalization in neurologically stable patients with blood pressure of >140/90 mmHg is recommended to improve long-term blood pressure control unless otherwise indicated 
• In patients with markedly elevated blood pressure, lower blood pressure by 10-15% during the first 24 hours after onset of stroke

Blood Pressure (mmHg)	Treatment
SBP >220 mmHg or DBP 121-140 mmHg	Labetalol: 10-20 mg IV over 1-2 minutes May repeat or double the dose every 10 minutes Max dose: 300 mg in 24 hours or Nicardipine: Initially, 5 mg/hr IV infusion; titrate to desired effect by increasing 2.5 mg/hr every 5 minutes Max dose: 15 mg/hr (Aim for 10-15% decrease in blood pressure)

• Blood pressure management of patients eligible for thrombolysis is critical before and during the administration of recombinant tissue plasminogen activator and during the ensuing 24 hours because severely elevated blood pressure is associated with parenchymal hemorrhage
• Thrombolysis is not performed in patients with SBP >185 mmHg or DBP >110 mmHg at the time of treatment
• Correct blood pressure using the following:

Blood Pressure (mmHg)

Treatment

SBP >185 mmHg or DBP >110 mmHg

Labetalol: 10-20 mg IV over 1-2 minutes; may repeat once or Nicardipine: 5 mg/hr IV infusion; titrate up to desired effect by 2.5 mg/hr at 5- to 15-minute intervals Max dose: 15 mg/hr When desired blood pressure is attained, adjust to maintain proper blood pressure level or Clevidipine: 1-2 mg/hr IV, titrate by doubling the dose every 2-5 minutes until desired BP is reached Max dose: 21 mg/hr or Other agents (eg Hydralazine, Enalapril)

• If blood pressure is not reduced and remains >185/110 mmHg despite treatment, DO NOT GIVE recombinant tissue plasminogen activator
  
• If medications are given to lower blood pressure, maintain the blood pressure level below 180/105 mmHg for at least the first 24 hours after IV recombinant tissue plasminogen activator treatment

Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator (rt-PA)

• rt-PA (Alteplase) is the only thrombolytic proven effective in the treatment of acute ischemic stroke to be administered ideally within 60 minutes of arrival of qualified patients
• Patients eligible for rt-PA should be treated as quickly as possible within the time window as the benefits of rt-PA diminish rapidly over time
• Carefully selected patients may have improved outcomes if treated within extended window of 3 to 4.5 hours of stroke symptom onset
• Administering within 4.5 hours of stroke symptom recognition may be beneficial in patients with acute ischemic stroke who awake with stroke symptoms or have unclear time of onset >4.5 hours from last known well or at baseline state and who have a DW-MRI lesion smaller than ⅓ of the middle cerebral artery territory and no visible signal change on FLAIR
• Intracranial hemorrhage can occur with use; risk can be reduced by careful selection of patients and presence of competent ancillary care
  
  • Signs and symptoms of intracranial hemorrhage following rt-PA include new headache, acute neurological deterioration, acute hypertension, nausea, or vomiting
  • Should intracranial hemorrhage be suspected, discontinue rt-PA and do CT scan or other tests to detect hemorrhage

• Angioedema is also a potential side effect which may cause partial airway obstruction
• Measure blood pressure and assess neurological status every 15 minutes during and after IV rt-PA infusion for 2 hours, then every 30 minutes for 6 hours, then hourly until 24 hours after IV rt-PA treatment
  • Blood pressure of <180/105 mmHg should be maintained for at least 24 hours after IV rt-PA
• Obtain follow-up CT or MRI at 24 hours after IV rt-PA before starting anticoagulants or antiplatelet agents
• Should be administered with or without multimodal CT, MRI and perfusion imaging
• Should be administered if patient is eligible even if mechanical thrombectomy is being considered

Endovascular Interventions

• Criteria for endovascular therapy with a stent retriever (all should be present):
  
  • A mRS score 0 to 1 prior to stroke
  • Causative occlusion of the internal carotid artery or proximal middle cerebral artery
  • Age ≥18 years
  • NIHSS score of ≥6
  • Alberta Stroke Program Early CT score (ASPECTS) of ≥6
  • Treatment can be initiated (groin puncture) within 6 hours of symptom onset

• Reduced time from symptom onset to reperfusion with endovascular therapies produces better clinical outcomes
  
  • Reperfusion to thrombolysis in cerebral infarction (TICI) grade 2b/3 should be achieved as early as possible and within 6 hours of stroke onset
  • It is not required to observe patients after IV rt-PA to assess for clinical response before pursuing endovascular therapy to achieve beneficial outcomes
• Endovascular therapy with intracranial thrombectomy may be considered in patients with anterior circulation occlusion who have contraindications for IV rt-PA if it can be completed within 6 hours of stroke symptom onset
  • May also be considered in patients <18 years with large vessel occlusion who can tolerate a groin puncture within 6 hours of stroke symptom onset

Other Options

• Mechanical or Endovascular Thrombectomy 
  • Mechanical thrombectomy is recommended in patients with acute ischemic stroke within 6-16 hours of last known normal who have large vessel occlusion in the anterior circulation and meet other DAWN or DEFUSE 3 eligibility criteria or acute ischemic stroke within 16-24 hours of last known normal who have large vessel occlusion in the anterior circulation and meet other DAWN eligibility criteria
  • Mechanical thrombectomy in posterior circulation stroke shows lower risk of symptomatic intracranial hemorrhage and benefits when started beyond 6 hours after symptom onset
  • Endovascular thrombectomy may be considered as treatment in eligible patients with acute basilar artery occlusion despite lack of a published randomized controlled trial to date
  • Studies have shown that endovascular thrombectomy within an extended time window (up to 24 hours) was beneficial in some selected patients 
  • Blood pressure should be maintained at <180/105 mmHg during and 24 hours after the procedure
• Intra-arterial Thrombolysis
  • Beneficial for patients with major ischemic strokes of <6 hours duration due to middle cerebral artery occlusion
• Intravenous Fibrinolytics
  • Tenecteplase may be used as an alternative to rt-PA in patients without contraindications to IV fibrinolysis who are eligible to undergo mechanical thrombectomy
  • May be considered as an alternative to rt-PA in patients with minor neurological deficit and no major intracranial occlusion
  • IV defibrinogenating agents or IV fibrinolytic agents other than Alteplase and Tenecteplase is not recommended

• Monitor blood pressure (BP) every 15 minutes for 2 hours from the start of recombinant tissue plasminogen activator therapy, then every 30 minutes for 6 hours, then every hour for the next 16 hours

Blood Pressure (mmHg)	Treatment
SBP >180-230 mmHg or DBP >105-120 mmHg	Labetalol: 10 mg IV followed by continuous IV infusion at 2-8 mg/min or Nicardipine: 5 mg/hr IV infusion initially, then titrate to desired effect by 2.5 mg/hr every 5-15 minutes Max dose: 15 mg/hr or Clevidipine: 1-2 mg/hr IV then titrate by doubling the dose every 2-5 minutes until desired BP Max dose: 21 mg/hr
SBP >230 mmHg or DBP 121-140 mmHg	Labetalol: 10-20 mg IV over 2 minutes May repeat every 10-20 minutes Max dose: 300 mg in 24 hours or Labetalol: 10 mg IV followed by continuous IV infusion at 2-8 mg/min Max dose: 300 mg in 24 hours or Nicardipine: 5 mg/hr IV infusion initially, then titrate to desired effect by 2.5 mg/hr every 5-15 minutes Max dose: 15 mg/hr or Clevidipine: 1-2 mg/hr IV then titrate by doubling the dose every 2-5 minutes until desired BP Max dose: 21 mg/hr

• If blood pressure is not controlled or DBP >140 mmHg, consider Sodium nitroprusside infusion at 0.5 mcg/kg/min (max dose: 10 mcg/kg/min)
  
• If medications are given to lower BP, maintain the BP level below 180/105 mmHg for at least the first 24 hours after IV recombinant tissue plasminogen activator treatment

Antiplatelet Agents

Aspirin

• Administered at a dose of 160-325 mg PO to most stroke patients and those who are not candidates for recombinant tissue plasminogen activator within 24-48 hours of stroke onset to prevent early recurrence, mortality and morbidity
  
  • For patients treated with recombinant tissue plasminogen activator, Aspirin should not be given within 90 minutes after the start of recombinant tissue plasminogen activator therapy
  • Contraindicated in patients with Aspirin allergy or suffering from gastrointestinal bleeding

• 21 days of dual antiplatelet therapy with Clopidogrel in minor stroke begun within 24 hours can be beneficial for early secondary stroke prevention for up to 90 days from onset of symptoms 
• Should not be used as a substitute if patient qualifies for other acute interventions (eg recombinant tissue plasminogen activator)

Anticoagulant Agents

Heparins

• Eg Unfractionated heparin (UFH), low-molecular-weight heparin and heparinoids
• Routine anticoagulation is not recommended
• Should not be used in lieu of recombinant tissue plasminogen activator for treatment of otherwise eligible patients
• Administration within 24 hours of recombinant tissue plasminogen activator is not recommended due to increased risk of bleeding complications
• Subcutaneous UFH and LMWH may be considered for deep venous thrombosis prophylaxis in at-risk patients
  
  • Non-pharmacologic treatments for deep venous thrombosis prevention may also be used
  • Risk vs benefit of pharmacologic agents needs to be considered

• Not shown to decrease mortality and morbidity nor prevent stroke recurrence