Paradoxical Emboli Account for 2-4% of All Embolic Ischemic CVA
Patients with paradoxical embolization are typically younger (mean age: 39) than patients with other types of arterial thromboembolization (mean age: 68)
Patients with paradoxical embolization typically have little evidence of cardiac or peripheral arterial disease
Mechanism: venous thrombosis that traverses a right-to-left intracardiac shunt (patent foramen ovale, atrial septal defect, atrial septal aneurysm)
Alberta Stoke Program Early CT Scan (ASPECTS) Study Using a Quantitative CT Score to Predict Outcome of Hyperacute Stroke Before Thrombolytic Therapy (Lancet, 2000) [MEDLINE]
Higher ASPECTS Score Correlates with Smaller Core Infarct
ASPECTS 6-7: moderate infarct core
ASPECTS ≥8: small infarct core
Baseline ASPECTS Score Correlated Inversely with Severity of Stroke on the National Institutes of Health Stroke Scale (NIHSS)
Baseline ASPECTS Score Predicted Functional Outcome (Sensitivity of 78%, Specificity of 96%) and Symptomatic Intracerebral Hemorrhage (Sensitivity of 90%, Specificity of 62%)
Recommendations for Diagnostic Imaging Evaluation in Patients with Acute Cerebral Ischemic Symptoms Which Have Not Yet Resolved (American Heart Association/American Stroke Association Acute Ischemic Stroke Guidelines, 2013) [MEDLINE]
Emergency Brain Imaging is Recommended Prior to Any Specific Therapy to Treat Ischemic Stroke (Class I, Level of Evidence A)
In Most Cases, Non-Contrast Head CT is Sufficient to Provide the Necessary Information to Make Decisions About Emergency Management
Either Non-Contrast Head CT or Brain MRI is Recommended Prior to Intravenous rtPA to Exclude Administration (Absolute Contraindication) and to Determine Whether CT Hypodensity or MRI Hyperintensity of Ischemia is Present (Class I, Level of Evidence A)
In Intravenous Thrombolytic Candidates, Brain Imaging Study Should Be Interpreted within 45 min of Patient Arrival in the Emergency Department by a Physician with Expertise in Reading CT/MRI Studies of the Brain Parenchyma (Class I, Level of Evidence C)
Head CT Perfusion and MRI Perfusion with Diffusion Imaging (Including Measures of Infarct Core and Penumbra) May Be Considered for the Selection of Patients for Acute Reperfusion Therapy Beyond the Time Windows for Intravenous Thrombolytics (Class IIb, Level of Evidence B)
These Techniques Provide Additional Information Which May Improve Diagnosis, Mechanism, and Severity of Ischemic Stroke and Allow More Informed Clinical Decision Making (Class IIb, Level of Evidence B)
Noninvasive Intracranial Vascular Study is Recommended During the Initial Imaging Evaluation of Acute Stroke if Either Intra-Arterial Thrombolytics or Mechanical Thrombectomy is Being Considered, But Should Not Delay the Initiation of Intravenous rtPA (Class I, Level of Evidence A)
Recommendations for Diagnostic Imaging Evaluation in Patients with Acute Cerebral Ischemic Symptoms Which Have Resolved (American Heart Association/American Stroke Association Acute Ischemic Stroke Guidelines, 2013) [MEDLINE]
Noninvasive Imaging of the Cervical Vessels Should Be Performed Routinely as Part of the Evaluation of Patients with Suspected TIA’s (Class I, Level of Evidence A)
Noninvasive Imaging (CTA or MRA) of the Intracranial Vasculature is Recommended to Exclude the Presence of Proximal Intracranial Stenosis and/or Occlusion and Should Be Obtained When the Knowledge of Intracranial Stenosis and/or Occlusion Will Alter Management (Class I, Level of Evidence A)
Reliable Diagnosis of the Presence/Degree of Intracranial Stenosis Requires Catheter Angiography to Confirm Abnormalities Detected with Noninvasive Testing
Patients with Transient Ischemic Neurologic Symptoms Should Undergo Neuroimaging Evaluation within 24 hrs of Symptom Onset (or as Soon as Possible in Patients with Delayed Clinical Presentation) Class I, Level of Evidence B)
MRI (Including Diffusion Weighted Imaging) is the Preferred Brain Diagnostic Imaging Modality (Class I, Level of Evidence B)
If MRI is Unavailable, Head CT Should Be Performed (Class I, Level of Evidence B)
Baseline EKG Assessment is Recommended in Patients Presenting with Acute Ischemic Stroke, But Should Not Delay the Initiation of Intravenous rtPA) (Class I, Level of Evidence B)
Although the Usefulness of Chest X-Ray in the Hyperacute Stroke Setting in the Absence of Acute Pulmonary/Cardiac/Pulmonary Vascular Disease is Unclear, it Should Not Delay the Initiation of Intravenous rtPA (Class IIb, Level of Evidence B)
Baseline Troponin is Recommended in Patients Presenting with Acute Ischemic Stroke, But Should Not Delay the Initiation of Intravenous rtPA) (Class I, Level of Evidence C)
Organized Protocol for the Emergency Evaluation of Patients with Suspected Stroke is Recommended (Class I, Level of Evidence B)
Goal is the Completion of Evaluation and Initiation of Thrombolytic Treatment within 60 min of Patient Arrival in the Emergency Department
Acute Stroke Team Should Include Physicians, Nurses, Laboratory Technicians, and Radiology Personnel
Careful Clinical Assessment (Including Neurologic Examination) is Recommended
Use of a Stroke Rating Scale is Recommended (Class I, Level of Evidence B)
NIHSS is the Preferred Stroke Scale
Diagnostic Testing: see above
Limited Number of Hematologic, Coagulation, and Biochemical Tests are Recommended During the Emergency Evaluation (and Only the Assessment of Blood Glucose Must Precede the Initiation of Intravenous rtPA) (Class I, Level of Evidence B)
Baseline EKG Assessment is Recommended in Patients Presenting with Acute Ischemic Stroke, But Should Not Delay the Initiation of Intravenous rtPA) (Class I, Level of Evidence B)
Baseline Troponin is Recommended in Patients Presenting with Acute Ischemic Stroke, But Should Not Delay the Initiation of Intravenous rtPA) (Class I, Level of Evidence C)
Although the Usefulness of Chest X-Ray in the Hyperacute Stroke Setting in the Absence of Acute Pulmonary/Cardiac/Pulmonary Vascular Disease is Unclear, it Should Not Delay the Initiation of Intravenous rtPA (Class IIb, Level of Evidence B)
Petechial Hemorrhage is Common with Ischemic Stroke Patients (without Associated Neurologic Deterioration) Who Have Not Been Treated with Reperfusion Therapies
Risk Factors for Hemorrhagic Transformation in Ischemic Stroke Patients Who Have Not Been Treated with Reperfusion Therapies Include Older Age, Larger Stroke, and Cardioembolic Source
Symptomatic Hemorrhagic Transformation Occurs in 5-6% of Ischemic Stroke Patients Who Have Been Treated with Reperfusion Therapies
Epidemiology: hypertension is common during acute ischemic stroke
Blood Pressure in Acute Ischemic Stroke is Often Higher in Patients with a History of Hypertension Than in Those Without a Premorbid History of Hypertension
One prospective study found a hazard ratio of 1.89 for the risk of poor outcome for each decrease in systolic BP of 10% in the first 24 hours
Another study found that the use of calcium channel blockers acutely lowered diastolic BP and was associated with worse outcomes
Clinical
Blood Pressure Typically Declines Spontaneously During the Acute Phase of an Ischemic Stroke, Starting Within 90 min After the Onset of Stroke Symptoms
Recommendations for Treating Hypertension in Stroke with Blood Pressure >185/110 mm Hg Prior to Acute Reperfusion Therapy (rtPA/Mechanical Thrombectomy)
Patients with Elevated Blood Pressure Who are Otherwise Eligible for Treatment with Intravenous rtPA Should Have Their Blood Pressure Carefully Lowered So that Their SBP is <185 mmHg and their DBP is <110 mm Hg Before Thrombolytics are Initiated (Class I, Level of Evidence B)
If Blood Pressure Cannot Be Maintained <185/110 mm Hg, Do Not Administer rtPA
If Antihypertensives are Given, BP Should Be Stabilized at the Lower Level Before Thrombolytics are Initiated and Maintained <180/105 mm Hg for at Least 24 hrs After rtPA Treatment (Class I, Level of Evidence B)
Until Other Data are Available, Blood Pressure Recommendations Above Should Be Followed for Patients Undergoing Acute Reperfusion Interventions Other than rtPA, Including Intra-Arterial Thrombolytics (Class I, Level of Evidence C)
Regimens
Labetalol (Normodyne, Trandate) IV (see Labetalol, Labetalol): 10-20 mg IV over 1-2 minutes -> may repeat x1
Nicardipine Drip (Cardene) (see Nicardipine, Nicardipine): 5 mg/h, titrate up by 2.5 mg/h at 5-15-min intervals (to max drip rate: 15 mg/hr) -> when desired BP attained, reduce to maintain proper BP limit
Recommendations for Treating Hypertension in Stroke During and After Acute Reperfusion Therapy (rtPA/Mechanical Thrombectomy)
Maintain BP ≤180/105 mm Hg During and After Acute Reperfusion Therapy for at Least 24 hrs After Treatment (Class I, Level of Evidence B)
BP Monitoring Paradigm
Monitor BP q15 min During Treatment and for Another 2 hrs
Monitor BP q30 min x 6 hrs
Monitor BP q1hr x 16 hrs
Regimens for SBP >180-230 mm Hg or DBP >105-120 mm Hg
Labetalol (Normodyne, Trandate) (see Labetalol, Labetalol): 10 mg IV over 1-2 min, followed by an infusion at 2-8 mg/min
Nicardipine Drip (Cardene) (see Nicardipine, Nicardipine): 5 mg/h, titrate up to desired effect by increasing 2.5 mg/h q5 min (to max drip rate: 15 mg/hr)
Recommendations for Treating Hypertension in Stroke Patients Not Undergoing Reperfusion Therapy
Until More Definitive Data are Available, the Benefit of Treating Arterial Hypertension in Acute Stroke is Not Well Established (Class IIb, Level of Evidence C)
Patients with Malignant Hypertension or Other Medical Indications for Aggressive Hypertension Treatment Should Be Treated Accordingly
In Patients with Marked Hypertension Who Do Not Receive Thrombolytics, a Reasonable Goal is to Lower the BP by 15% During the First 24 hrs After the Onset of Stroke (Class I, Level of Evidence C)
By Consensus, Antihypertensives Should Be Withheld Unless the SBP is >220 mm Hg or the DBP is >120 mm Hg (Class I, Level of Evidence C)
Recommendations Regarding Specific Antihypertensive Medications to Treat Hypertension in Stroke
No Data are Available to Guide the Selection of Medications for the Lowering of Blood Pressure in Stroke (Class IIa, Level of Evidence C)
The Antihypertensive Medications/Doses Above are Reasonable Choices Based on General Consensus (Class IIa, Level of Evidence C)
Recommendations for Restarting Antihypertensive Therapy After Stroke
Evidence from One Clinical Trial Indicates that the Initiation of Antihypertensive Therapy within 24 hrs of Stroke is Relatively Safe
Restarting Antihypertensive Therapy is Reasonable After the First 24 hrs for Patients Who Have Preexisting Hypertension and are Neurologically Stable Unless a Specific Contraindication Exists (Class IIa, Level of Evidence B)
Cardiovascular/Hemodynamic Management
Clinical Efficacy
Cochrane Database Systematic Review Comparing Types of Fluid Resuscitation in Acute Ischemic/Hemorrhagic Stroke (Cochrane Database Syst Rev, 2015) [MEDLINE]
Odds of Death or Dependence were Similar for Crystalloids and Colloids
Odds of Pulmonary Edema were Higher with Colloids
No Data was Available to Guide the Optimal Volume, Duration, or Mode of Parenteral Fluid Delivery in Acute Stroke
General Recommendations
Phlebotomy is Not Recommended
Hydration with Normal Saline is Recommended (Emerg Med Clin North Am, 2012) [MEDLINE]
Avoid Hypotonic Intravenous Fluids, Since These May Exacerbate Cerebral Edema and are Less Effective in Replacing Intravascular Volume
Avoid Dextrose-Containing Fluids, Since Glucose May Exacerbate Hyperglycemia
Hypovolemia Should Be Corrected with Intravenous Normal Saline (Class I, Level of Evidence C)
Cardiac Monitoring is Recommended to Screen for Atrial Fibrillation and Other Potentially Serious Cardiac Arrhythmias Which Might Necessitate Emergency Cardiac Interventions (Class I, Level of Evidence B)
Cardiac Monitoring Should Be Performed for at Least the First 24 hrs (Class I, Level of Evidence B)
Cardiac Arrhythmias Which Might Decrease Cardiac Output Should Be Corrected (Class I, Level of Evidence C)
Hemodilution by Volume Expansion is Not Recommended in Acute Ischemic Stroke (Class III, Level of Evidence A)
Usefulness of Drug-Induced Hypertension in Acute Ischemic Stroke is Not Established and Should Only Be Performed in the Setting of Clinical Trials (Class IIb, Level of Evidence B)
In Exceptional Cases with Systemic Hypotension Producing Neurologic Sequelae, Vasopressors May Be Used to Improve Cerebral Blood Flow
If Drug-Induced Hypertension is Utilized, Close Neurologic and Cardiac Monitoring are Recommended (Class I, Level of Evidence C)
Infuse rtPA at 0.9 mg/kg (Max Dose: 90 mg) over 1 hr with 10% of the Dose Given as a Bolus Over 1 min
Admit the Patient to an ICU/Stroke Unit for Monitoring
Perform Neurologic Assessments q15 min During the rtPA Infusion and q30 min x 6 hours, then q1hr x 24 hrs After Infusion
If the Patient Develops Severe Headache/Acute Hypertension/Nausea or Vomiting, Discontinue the rtPA infusion and Obtain a Stat Head CT
Measure Blood Pressure q15 min for the First 2 hrs, q30 min x 6 hrs -> q1hr x 24 hrs After Treatment
Increase the Frequency of Blood Pressure Measurement for SBP >180 mm Hg or DBP >105 mm Hg
Administer Antihypertensives to Maintain Blood Pressure at or Below These Levels
Delay Placement of NG Tubes, Foley Catheters, or Intra-Arterial Pressure Catheters if the Patient Can Be Safely Managed without Them
Obtain a Follow-Up Head CT or Brain MRI Scan at 24 hrs After rtPA Before Starting Anticoagulants or Anti-Platelet Agents
Clinical Efficacy
ECASS Trial of Thrombolytics in Stoke Between 3-4.5 hrs (NEJM, 2008) [MEDLINE]
Intravenous Alteplase Significantly Improved Outcome When Administered Between 3-4.5 hrs in Acute Ischemic Stroke
Intravenous Alteplase Increased the Risk of Symptomatic Intracranial Hemorrhage
Study of the Real-World Recanalization Rates Following Intravenous Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke (Stroke, 2010) [MEDLINE]
Low Recanalization Rates
Distal Internal Carotid Artery (ICA): 4.4%
Basilar Artery: 4%
Middle Cerebral Artery (MCA) M1 and M2 Segments: 30%
Emergency Brain Imaging is Recommended Prior to Any Specific Therapy to Treat Ischemic Stroke (Class I, Level of Evidence A)
In Most Cases, Non-Contrast Head CT is Sufficient to Provide the Necessary Information to Make Decisions About Emergency Management
Either Non-Contrast Head CT or Brain MRI is Recommended Prior to Intravenous rtPA to Exclude Administration (Absolute Contraindication) and to Determine Whether CT Hypodensity or MRI Hyperintensity of Ischemia is Present (Class I, Level of Evidence A)
Intravenous Thrombolytic Therapy is Recommended in the Setting of Early Ischemic Changes (Other than Frank Hypodensity) on Head CT, Regardless of Their Extent (Class I, Level of Evidence A)
Frank Hypodensity on Non-Contrast Head CT May Increase the Risk of Hemorrhage with Thrombolytics and Should Be Considered in Treatment Decisions (Class III, Level of Evidence A)
If Frank Hypodensity Involves >33% of the Middle Cerebral Artery Territory, Intravenous rtPA Treatment Should Be Withheld (Class III, Level of Evidence A)
Intravenous rtPA is Reasonable in Patients Whose Blood Pressure Can Be Lowered Safely and Stably (to <185/110 mm Hg) with Antihypertensive Agents Prior to Initiation of rtPA (Class I, Level of Evidence B)
Intravenous rtPA is Reasonable in Patients with a Seizure at the Time of Onset of Stroke if Evidence Suggests that the Residual Neurologic Impairments are Due to the Stroke and Not a Postictal Phenomenon (Class IIa, Level of Evidence C)
Intravenous rtPA (0.9 mg/kg, Max Dose: 90 mg) is Recommended for Selected Patients Who Can Be Treated within 3 hrs of Onset of Ischemic Stroke (Class I, Level of Evidence A)
General
Benefit of rtPA Therapy is Time-Dependent and Treatment Should Be Initiated as Quickly as Possible (Class I, Level of Evidence A)
The Hospital Door-to-Time of Bolus Administration Latency Should Be <60 min (Class I, Level of Evidence A)
Use of rtPA in Patients on Direct Oral Anticoagulants (Thrombin Inhibitors, Factor Xia Inhibitors) May Be Harmful and is Not Recommended Unless Sensitive Laboratory Tests (INR, PTT, Thrombin Time, Platelet Count, ECT, or Factor Xa Activity Assay) are Normal or the Patient Has Been Off of the Medication for >2 Days (with Normal Renal Function) (Class III, Level of Evidence C)
Similar Cautions Should Be Exercised for Patients Who are Being Considered for Other Reperfusion Therapies (Class III, Level of Evidence C)
Use of rtPA in Patients <3 hrs from Symptom Onset and the Relative Exclusion Criteria Below Should Be Carefully Considered with Regard to Risks/Benefits of Treatment (Class IIb, Level of Evidence C)
Inclusion Criteria
Age ≥18 y/o
Ischemic Stroke with Measurable Neurological Deficit
Seizure at Onset with Postictal Residual Neurologic Impairment (see Seizures, Seizures)
Intravenous rtPA (0.9 mg/kg, Max Dose: 90 mg) is Recommended for Selected Patients Who Can Be Treated within 3-4.5 hrs of Onset of Ischemic Stroke (Class I, Level of Evidence B)
Effectiveness of rtPA is Not Well Established for Patients Between 3-4.5 hrs of Symptom Onset and the Relative Exclusion Criteria Below (Class IIb, Level of Evidence C)
Inclusion Criteria
Ischemic Stroke with Measurable Neurological Deficit
Symptom Onset within 3-4.5 hrs
Relative Exclusion Criteria
Age >80 y/o
Anticoagulation with Oral Agent (and Any INR)
History of Both Diabetes Mellitus and Prior Ischemic Stroke
Severe Stroke (NIHSS >25)
In Patients Undergoing rtPA Therapy, Providers Should Be Aware of and Able to Treat Potential Complications (Bleeding, Angioedema, etc) (Class I, Level of Evidence B)
Use of Other Therapies
The Usefulness of Intravenous Tenecteplase/Reteplase/Desmoteplase/Urokinase/Other Fibrinolytic Agents and Intravenous Ancrod/Other Defibrinogenating Agents is Not Well Established (Class IIb, Level of Evidence B)
These Agents Should Only Be Used in the Setting of a Clinical Trial (Class IIb, Level of Evidence B)
Streptokinase is Not Recommended for Acute Stroke (Class III, Level of Evidence A)
Effectiveness of Sonothrombolysis for Acute Stroke is Not Well Established (Class IIb, Level of Evidence B)
Endovascular Therapy
Clinical Efficacy
Worldwide ESCAPE Trial of Endovascular Therapy in Acute Ischemic CVA (NEJM, 2015) [MEDLINE]: usual care (control) vs usual care and endovascular treatment with thrombectomy devices (intervention)
Endovascular Treatment Improved Outcome in Patients with Proximal Vessel Occlusion, a Small Infarct Core, and Moderate-to-Good Collateral Circulation
Dutch MR CLEAN Trial of Intra-Arterial Endovascular Therapy in Acute Ischemic CVA (NEJM, 2015) [MEDLINE]: usual care (control) vs usual care and intra-arterial treatment
In Acute Ischemic CVA Due to a Proximal Intracranial Occlusion of the Anterior Circulation, Intra-Arterial Treatment within 6 hrs was Effective and Safe
Systematic Review of Acute Stroke Interventions (JAMA, 2015) [MEDLINE]
Systemic tTPA Remains the Standard of Care for Patients with Moderate-Severe Neurologic Deficits Who Present Within 4.5 hrs of Symptom Onset
Patients with Ischemic CVA with Moderate-Severe Neurologic Deficits Due to Proximal Artery Occlusion are Improved with Endovascular Therapy
SWIFT PRIME Trial of Stent Retriever Thrombectomy as Add-On Therapy to Intravenous Thrombolytics in Acute CVA (NEJM, 2015) [MEDLINE]
In Patients with Proximal Anterior Intracranial Circulation Stroke Treated within 6 hrs of Symptom Onset, Stent Retriever Thrombectomy Improve 90-Day Functional Outcome
Australian EXTEND-IA Trial of Solitaire FR (Flow Restoration) Stent Retriever Thrombectomy as Add-On Therapy to Intravenous Thrombolytics in Acute CVA (NEJM, 2015) [MEDLINE]
In Patients with Proximal Cerebral Arterial Occlusion and Salvageable Tissue on CT Perfusion Imaging, Early Thrombectomy with the Solitaire FR (Flow Restoration) Stent Retriever Improved Reperfusion, Early Neurologic Recovery, and Functional Outcome Over Alteplase Alone
Spanish REVASCAT Trial of Solitaire Stent Retriever Thrombectomy as Add-On Therapy to Intravenous Thrombolytics in Acute Ischemic CVA within 8 hrs (N Engl J Med, 2015) [MEDLINE]: study was terminated early (due to the benefits observed in the similar ESCAPE, EXTEND IA, and MR CLEAN trials)
In Patients with Anterior Circulation Stroke Who Could Be Treated within 8 hrs of Symptom Onset, Solitaire Stent Retriever Thrombectomy Decreased the Severity of Post-Stroke Disability and Increased the Rate of Functional Independence
Revascularized TICI 2b-3 Flow (Thrombolysis in Infarction Score; 2b = Complete Filling of All of the Expected Vascular Territory is Visualized, But the Filling is Slower than Normal; 3 = Complete Perfusion, Antegrade Flow into the Bed Distal to the Obstruction Occur) was 65.7% in the Intervention Group
No Difference in Mortality Rates Between the Groups
No Difference in Symptomatic Intracranial Hemorrhage Between the Groups
Selected Recommendations (American Heart Association Stroke Council Focused 2015 Update of 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment) [MEDLINE]
Patients Eligible for Intravenous tPA Should Receive Intravenous tPA Even if Endovascular Therapy is Being Considered (Class I, Level A)
Observing the Patient After tPA for Clinical Improvement Prior to Endovascular Therapy is Not Required (Class III, Level B-NR)
If Endovascular Therapy is Being Considered, a Non-Invasive Intracranial Vascular Imaging Study is Recommended if Not Already Performed as Part of the Initial Stroke Evaluation (Class I, Level A):
However, this Study Should Not Delay the Initiation of Intravenous tPA Therapy
Patients Should Receive Endovascular Therapy with Stent Retriever if They Meet the Following Criteria (Class I, Level A): patients who do not meet all of these criteria may also be considered, but evidence is less clear in these cases
Acute Ischemic CVA within 4.5 hrs of Onset
Age ≥18 y/o
Occluded Internal Carotid or Proximal MCA (M1)
ASPECTS ≥6
NIHSS ≥6
Prestroke mRS 0-1
Availability of Treatment Initiation (Groin Puncture) Within 6 hrs of Symptom Onset: decreased time from symptom onset to reperfusion is associated with better outcome (Class I, Level B-R)
Benefit of Endovascular Therapy After 6 hrs From Symptom Onset (in Internal Carotid or Proximal MCA-M1) is Uncertain (Class IIb, Level C)
Selected Patients with Anterior Circulation Occlusions with Contraindications to tPA and Within 6 hrs of Symptom Onset Can Be Considered for Endovascular Therapy with Stent Retriever (Class IIa, Level C)
In Patients with MCA-M2 or M3/Anterior Cerebral/Vertebral/Basilar/Posterior Cerebral Artery Occlusions, There is Unclear Clinical Benefit for Use of Endovascular Therapy with Stent Retrievers Within 6 hrs of Symptom Onset (Class IIb, Level C)
Use of Endovascular Stent Retrievers is Preferred Over MERCI Device (Class IIb, Level B-NR)
Use of Endovascular Stent Retrievers is Preferred Over Intra-Arterial Thrombolytics (Class I, Level E)
Oral Aspirin (Initial Dose: 325 mg) is Recommended within 24-48 hrs After Stroke Onset (Class I, Level of Evidence A)
Administration of Aspirin (or Other Antiplatelet Agents) as an Adjunctive Therapy within 24 hrs of Intravenous rtPA is Not Recommended (Class III, Level of Evidence C)
Aspirin is Not Recommended as a Substitute for Other Acute Interventions in Stroke, Including Intravenous rtPA (Class III, Level of Evidence B)
Other Agents
Usefulness of Clopidogrel for the Treatment of Acute Ischemic Stroke is Not Well Established (Class IIb, Level of Evidence C)
Efficacy of intravenous Tirofiban and Eptifibatide is Not Well Established and These Agents Should Only Be Used in the Setting of Clinical Trials (Class IIb, Level of Evidence C)
Administration of Other Intravenous Antiplatelet Agents Which Inhibit the Glycoprotein IIb/IIIa Receptor is Not Recommended (Class III; Level of Evidence B)
Anticoagulation
Clinical Efficacy
Early Administration of Either Unfractionated Heparin or Low Molecular Weight Heparin is Associated with an Increased Risk of Bleeding Complications in Acute Stroke
Data are Unclear as to Whether Anticoagulation Might Be Effective in High-Risk Groups (Such as Patients with Intracardiac or Intra-Arterial Thrombi)
The Effectiveness of Anticoagulation for Patients with Arterial Dissection or Vertebrobasilar Disease is Not Established
The Role of Anticoagulation as an Adjunct to Mechanical/Pharmacologic Thrombolysis is Not Established
Urgent Anticoagulation, with the Goal of Preventing Early Recurrent Stroke, Halting Neurologic Worsening, or Improving Outcome After an Acute Ischemic Stroke is Not Recommended (Class III, Level of Evidence A)
Usefulness of Urgent Anticoagulation in Patients with Severe Internal Carotid Artery Stenosis Ipsilateral to an Ischemic Stroke is Not Well Established (Class IIb, Level of Evidence B)
Initiation of Anticoagulation within 24 hrs of Intravenous rtPA Treatment is Not Recommended (Class III, Level of Evidence B)
Urgent Anticoagulation for the Management of Non-Cerebrovascular Conditions is Not Recommended for Patients with Moderate-Severe Strokes Due to an Increased Risk of Serious Intracranial Hemorrhage (Class III, Level of Evidence A)
Use of Argatroban or Other Thrombin Inhibitors for Acute Ischemic Stroke is Not Well Established and These Agents Should Only Be Used in the Setting of Clinical Trials (Class IIb, Level of Evidence B)
Pooled Analysis of DECIMAL/DESTINY/HAMLET Trials in Malignant Middle Cerebral Artery Infarction (Lancet Neurol, 2007) [MEDLINE]
Decompressive Craniectomy Within 48 hrs of Stroke Onset Decreased Mortality and Increased the Number of Patients with a Favorable Functional Outcome
Decision to Perform Decompressive Craniectomy Should Be Made on an Individual Basis for Each Patient
DESTINY II Trial in Malignant Middle Cerebral Artery Infarction (NEJM, 2014) [MEDLINE]
Decompressive Craniectomy Improved Survival Without Severe Disability in Patients >61 y/o with Middle Cerebral Artery Infarction, as Compared to Control
Survival with No Disability or Slight Disability (Rankin = 0-2)
Decompressive Craniectomy: 0%
Control: 0%
Moderate Disability (Rankin = 3)
Decompressive Craniectomy: 7%
Control: 3%
Moderately Severe Disability with Requirement for Assistance with Most Bodily Needs (Rankin = 4)
Decompressive Craniectomy: 32%
Control: 15%
Severe Disability (Rankin = 5)
Decompressive Craniectomy: 28%
Control: 13%
Conclusion: the majority of survivors required assistance with most bodily needs
Since Patients with Large Infarctions are at High Risk for Cerebral Edema and Increased Intracranial Pressure, Measures to Lessen the Risk of Edema and Close Monitoring for Signs of Neurological Worsening During the First Days After Stroke are Recommended (Class I, Level of Evidence A)
Early Transfer of Patients at Risk for Significant Cerebral Edema to an Institution with Neurosurgical Expertise Should Be Considered
Corticosteroids (in Conventional or Large Doses) are Not Recommended for Cerebral Edema/Increased Intracranial Pressure Due to Ischemic Stroke, Due to Lack of Defined Efficacy and Risk for Infectious Complications (Class III, Level of Evidence A)
Decompressive Surgical Evacuation of a Space-Occupying Cerebellar Infarction is Effective in Preventing and Treating Herniation and Brainstem Compression (Class I, Level of Evidence B)
Decompressive Surgery for Malignant Cerebral Edema of the Cerebral Hemisphere is Effective and Potentially Lifesaving (Class I, Level of Evidence B)
Advanced Patient Age and Patient/Family Valuations of Achievable Outcome May Affect Decisions Regarding this Procedure
Although Aggressive Medical Measures Have Been Recommended for Malignant Cerebral Edema After A Large Cerebral Infarction, Usefulness of These Measures is Not Well Established (Class IIb, Level of Evidence C)
Usefulness of Emergent/Urgent CEA When Clinical Indicators or Brain Imaging Suggests a Small Infarct Core with Large Territory at Risk (Penumbra), Compromised by Inadequate Flow from a Critical Carotid Stenosis or Occlusion (or in the Case of Acute Neurological Deficit after CEA in Which Acute Thrombosis of the Surgical Site is Suspected) is Not Well Established (Class IIb, Level of Evidence B)
In Patients with Unstable Neurologic Status (Stroke-in-Evolution or Crescendo TIA’s), the Efficacy of Emergent/Urgent CEA is Not Well Established (Class IIb, Level of Evidence B)
Prophylactic Use of Anticonvulsants is Not Recommended (Class III, Level of Evidence C)
Recurrent Seizures After Stroke Should Be Treated Similarly to Other Acute Neurologic Conditions and Anticonvulsant Agents Should Be Selected by Specific Patient Characteristics (Class I, Level of Evidence B)
Since Evidence Indicates that Persistent In-Hospital Hyperglycemia During the First 24 hrs Post-Stroke is Associated with Worse Outcomes than Normoglycemia, Treating Hyperglycemia to Achieve Blood Glucose Level 140-180 mg/dL (and Prevention of Hypoglycemia) is Recommended in Acute Stroke (Class IIa, Level of Evidence C)
Hypoglycemia (Blood Glucose <60 mg/dL) Should Be Treated in Patients with Acute Stroke (Class I, Level of Evidence C)
Pharmacologic Deep Venous Thrombosis (DVT) Prophylaxis is Recommended (Class I, Level of Evidence A)
Use of Intermittent External Compression Devices is Reasonable for Deep Venous Thrombosis (DVT) Prophylaxis in Patients Who Cannot Receive Anticoagulants (Class IIa; Level of Evidence B)
Use of Aspirin is Reasonable for Deep Venous Thrombosis (DVT) Prophylaxis in Patients Who Cannot Receive Anticoagulants (Class IIa, Level of Evidence A)
Assessment of Swallowing Before the Patient Begins Eating/Drinking/Receiving Oral Medications is Recommended (Class I, Level of Evidence B)
Patients Who Cannot Take Solid Food/Liquids Orally Should Receive Tube Feedings (Via Nasogastric/Nasoduodenal/Gastrostromy Route) to Maintain Hydration and Nutrition While Undergoing Efforts to Restore Swallowing Function (Class I, Level of Evidence B)
In Selecting the Route of Enteral Feeding (Nasogastric vs Gastrostomy) in Patients Who Cannot Take Solid Foods or Liquids Orally, it is Reasonable to Utilize the Nasogastric Route Until 2-3 wks After Stroke Onset (Class IIa, Level of Evidence B)
Routine Use of Nutritional Supplements Has Not Been Demonstrated to Be Beneficial (Class III, Level of Evidence B)
Supplemental Oxygen Should Be Provided to Maintain SaO2 >94% (Class I, Level of Evidence C)
Supplemental Oxygen is Not Recommended in Normoxemic Patients with Acute Ischemic Stroke (Class III, Level of Evidence B)
Airway Support/Ventilatory Assistance are Recommended for Acute Stroke Patients with Depressed Consciousness or Bulbar Dysfunction with Airway Compromise (Class I, Level of Evidence C)
Patients with Suspected Pneumonia or UTI Should Be Treated with Appropriate Antibiotics (Class I, Level of Evidence A)
In Patients Already Taking a Statin at the Time of Onset of Acute Ischemic Stroke, Continuation of Statin Therapy During the Acute Period is Reasonable (Class IIa, Level of Evidence B)
Early Mobilization of Less Severely Affected Patients and Measures to Prevent the Subacute Complications of Stroke are Recommended (Class I, Level of Evidence C)
Other Treatments with Unclear or No Proven Efficacy in Stroke
Administration of High-Dose Albumin is Not Well Established in Acute Ischemic Stroke Until Further Definitive Evidence Regarding Efficacy Becomes Available (Class IIb, Level of Evidence B)
Use of Devices to Augment Cerebral Blood Flow in Acute Ischemic Stroke is Not Well Established and Should Only Be Used in the Setting of Clinical Trials (Class IIb, Level of Evidence B)
Data on the Utility of Hyperbaric Oxygen in Acute Stroke are Inconclusive
Some Data and Imply that Hyperbaric Oxygen in Acute Stroke May Be Harmful in Acute Stroke and it is Therefore Not Recommended (Class III, Level of Evidence B)
At Present, No Pharmacological Agents with Putative Neuroprotective Actions Have Been Demonstrated to Have Efficacy in Improving Outcome After Ischemic Stroke and These are Therefore Not Recommended (Class III, Level of Evidence A)
At Present, Transcranial Near-Infrared Laser Therapy is Not Well Established for the Treatment of Acute Ischemic Stroke and Further Trials are Recommended (Class IIb, Level of Evidence B)
References
General
Validity and reliability of a quantitative computed tomography score in predicting outcome of hyperacute stroke before thrombolytic therapy. ASPECTS Study Group. Alberta Stroke Programme Early CT Score. Lancet 2000;355(9216):1670-1674 [MEDLINE]
Early recurrent ischemic stroke in stroke patients undergoing intravenous thrombolysis. Circulation. 2006;114:237-241 [MEDLINE]
Clinical
Continuous pulse oximetry in acute hemiparetic stroke. J Neurol Sci. 2000;179(S 1–2):65–69 [MEDLINE] - Unexpected nocturnal hypoxia in patients with acute stroke. Stroke. 2003;34:2641–2645 [MEDLINE]
Nosocomial pneumonia after acute stroke: implications for neurological intensive care medicine. Stroke. 2003;34:975–981 [MEDLINE]
Treatment
The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet. 1997;349:1569-1581 [MEDLINE]
The effect of combined thrombolysis with rtPA and tirofiban on ischemic brain lesions. Neurology. 2004;62:2110-2112
Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007;38:1655-1711 [MEDLINE]
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Hyperthermia and fever control in brain injury. Crit Care Med 2009;37(7):S250-57 [MEDLINE]
The hydration influence on the risk of stroke (THIRST) study. Neurocrit Care. 2009;10(2):187-94. Epub 2008 Dec 3 [MEDLINE]
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Parenteral fluid regimens for improving functional outcome in people with acute stroke. Cochrane Database Syst Rev. 2015 Sep 1;9:CD011138. doi: 10.1002/14651858.CD011138.pub2 [MEDLINE]
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MR CLEAN Trial: A randomized trial on intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015;372:11–20 [MEDLINE]
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Anticoagulants for acute ischaemic stroke. Cochrane Database Syst Rev. 2015 Mar 12;3:CD000024. doi: 10.1002/14651858.CD000024.pub4 [MEDLINE]
Blood Pressure in Acute Ischemic Stroke. J Clin Neurol. 2016 Apr;12(2):137-46. doi: 10.3988/jcn.2016.12.2.137. Epub 2016 Jan 28 [MEDLINE]
Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2016 Feb;47(2):581-641. doi: 10.1161/STR.0000000000000086. Epub 2015 Dec 22 [MEDLINE]
ECASS Trial. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656 [MEDLINE]
Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke. 2010 Oct;41(10):2254-8. doi: 10.1161/STROKEAHA.110.592535. Epub 2010 Sep 9. [MEDLINE]
Endovascular Therapy
American Heart Association Stroke Council. Focused update of 2013 guidelines for the early management of patients with acute stroke regarding endovascular treatment. Stroke 2015;46:3020–3035 [MEDLINE]
Endovascular therapy for stroke—it’s about time. N Engl J Med. 2015;372:2347–2349 [MEDLINE]
REVASCAT Trial. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015;372:2296–2306 [MEDLINE]
SWIFT PRIME Trial. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17 [MEDLINE]
ESCAPE Trial: Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372:1019–1030 [MEDLINE]
EXTEND-IA Trial. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372:1009–1018 [MEDLINE]
Mechanical Thrombectomy Is Now the Gold Standard for Acute Ischemic Stroke: Implications for Routine Clinical Practice. Interv Neurol. 2015 Oct;4(1-2):18-29. doi: 10.1159/000438774. Epub 2015 Sep 18 [MEDLINE]
Decompressive Craniectomy
DECIMAL, DESTINY, and HAMLET investigators. Early decompressive surgery in malignant middle cerebral artery infarction: a pooled analysis of three randomised controlled trials. Lancet Neurol. 2007; 6:215–222 [MEDLINE]
Early decompressive hemicraniectomy in older patients with nondominant hemispheric infarction improves outcome. Stroke 2011; 42:843-844 [MEDLINE]
DESTINY II Trial. Hemicraniectomy in older patients with extensive middle-cerebral-artery stroke. N Engl J Med. 2014 Mar 20;370(12):1091-100. doi: 10.1056/NEJMoa1311367 [MEDLINE]
