Standard strategies for acute ischemic stroke within the rtPA therapeutic window

A 63-year-old hypertensive, diabetic man called 911 at 8:00 PM complaining of right-sided weakness that started at 6:30 PM after dinner. The ambulance arrived at the patient's house at 8:05 PM and he was brought to the nearest stroke center. While en route, the paramedic alerted the stroke center emergency department. The patient arrived at the emergency room at 8:30 PM and was immediately evaluated by the physician. A stroke code was called and the neurologist was at the bedside at 8:40 PM. An 18-gauge IV was inserted by the nurse and blood test for basic metabolic panel, complete blood count, coagulopathy panel, and lipid profile were sent. The NIH Stroke Scale was performed, showing a total score of 10. The time of onset was verified with the patient's wife, who witnessed the event. A noncontrast CT was done at 8:50 PM and officially read at 8:55 PM, showing absence of signs of hemorrhage or acute infarct. After reviewing the inclusion and exclusion criteria, the patient was deemed eligible for thrombolysis and IV tissue plasminogen activator (tPA) was ordered. The IV tPA was initiated at 9:15 PM, 45 minutes from the time the patient entered the emergency room door, 2 hours and 45 minutes from symptom onset. This scenario is increasingly becoming a routine exercise in many primary stroke centers across the United States.

In the United States, patients with measurable deficit are treated with IV tPA within 3 hours of symptoms. Since 2008, many stroke neurologists have extended the treatment window for IV tPA to 4.5 hours as long as the patient fulfills additional criteria as used in the European Cooperative Acute Stroke Study 3 trial,1 despite lack of approval by the Food and Drug Administration (FDA). In addition to IV tPA, patients in comprehensive stroke centers are evaluated further using multimodality imaging using CT or MRI to locate the stenosis or occlusion (CT or MRI angiography of the head and neck) and to quantify the infarct and estimate the size of the ischemic penumbra (CT or MRI perfusion). These additional imaging techniques are incorporated in the emergency imaging of acute stroke patients and done immediately after the noncontrast CT, while the patient is receiving IV tPA. Whether perfusion imaging is useful in clinical decision-making is uncertain. Carefully selected patients with acute occlusion or severe stenosis of intracranial vessels are immediately sent for diagnostic catheter angiography for mechanical thrombectomy or intraarterial thrombolysis. Three devices are currently FDA-approved for intracranial reperfusion: MERCI (2004), Penumbra (2007), and Solitaire (2012). Patients with stroke onset within 8 hours (longer for posterior circulation strokes) are considered for endovascular intervention if large ischemic penumbra is seen on perfusion imaging (at least 20% perfusion mismatch) especially if the infarct core/volume is less than 100 mL.

Blood pressure (BP) medications are typically withheld in the acute phase of stroke, and no intervention is done unless systolic BP goes over 185 mm Hg in patients receiving IV tPA or 220 mm Hg in patients not receiving IV tPA. Acute IV anticoagulation with heparin is not done except in some patients with extracranial arterial dissection. Patients are admitted to the stroke unit if stable, or to the neurocritical care unit if hemodynamically unstable or requiring ventilator support. Antiplatelet medications are started within 24 hours or after 24 hours of IV tPA. Patients are discharged on oral anticoagulation without bridging if atrial fibrillation is identified. Diabetic education and medications are given as necessary with goal glycosylated hemoglobin (HBA1C) of <7%. High-dose statin is given to keep low-density lipoprotein under 100 mg/dL (<70 if the patient has diabetes or coronary artery disease).

The availability of emergency notification using the 911 telephone system (which covers over 96% of the US population) and the proliferation of certified stroke centers across the country (approximately 1 out of 4 acute care hospitals in the United States in 20102 were certified stroke centers, and more than 80% of the US population were within 1 hour's drive from the nearest stroke center) has helped in increasing the use of IV tPA among eligible patients (currently about 75% of eligible patients receive IV tPA3). Certified stroke centers are evaluated based on established performance measures including strict time targets for every segment of emergency stroke management. The current goal is for all eligible stroke patients to be treated with IV thrombolysis within 60 minutes from arrival to the emergency room. Key time targets in the process include performance of patient evaluation by physician within 10 minutes, stroke code activation within 15 minutes, performance of CT or MRI scan within 25 minutes, and interpretation of brain imaging within 45 minutes of patient presentation.

Ambulances transporting acute stroke patients may bypass the nearest hospital to a certified stroke center if the patient can arrive within 2 hours from symptom onset. Some states even have laws mandating this process. Some hospitals without primary stroke center certification have established transfer agreement and referral system with the nearest stroke center either via telemedicine or regular phone consultation with variable capability for remote imaging review by consultant stroke neurologist.

The standard approach in acute stroke management is relatively uniform for hospitals that have received stroke center certification in either rural or urban hospital settings. Due to increased reimbursement rate for patients treated with thrombolysis, there is financial incentive for hospitals to have stroke center certification and avoid being bypassed by ambulances with potential stroke patients. More importantly, patients admitted to stroke centers have improved outcome in terms of reduced 30-day risk of mortality, greater use of thrombolytics, and higher adherence to accepted treatment guidelines.4

Despite significant advancement in standardization of acute stroke therapy, variability continues to exist in availability of services and clinical outcome geographically (Stroke Belt) and temporal factors (weekend vs weekday) as well as IV tPA use. Continued development of organized stroke care with the recent introduction of comprehensive stroke center certification is showing promise in reducing this variability.5

Correspondence to: latorrej@upstate.edu