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Identifying and Treating Acute Ischemic Stroke



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Am Fam Physician. 1998 Apr 15;57(8):1965-1968.

Effective treatment of acute ischemic stroke requires rapid assessment and early intervention. Currently, the only effective therapy is thrombolysis with tissue plasminogen activator (tPA) within three hours after the onset of stroke. However, a number of potential delays make early diagnosis and treatment difficult. Kasner and Grotta review the pathophysiology of cerebral ischemia and the implications for treatment, identify some of the potential delays that commonly occur in diagnosing stroke and offer ways to expedite diagnosis and treatment.

Stroke occurs as a result of a specific sequence of events that happen after abrupt interruption of blood flow to the brain. The level of brain injury depends on the severity and duration of ischemia. In the hours after stroke, cytokines and cell adhesion molecules stimulate local inflammation, which further impairs blood flow. Reperfusion must occur within three hours of the onset of symptoms to preserve a substantial portion of the brain tissue at risk.

Treatment of acute stroke focuses on restoring cerebral perfusion and protecting neural tissue. Thrombolysis with tPA has demonstrated a positive effect on reperfusion since tPA converts plasminogen to plasmin, which causes cleavage of fibrin and ultimately results in rapid lysis of the clot. At this time, neuro-protective therapies and streptokinase are not effective in the treatment of acute stroke. For tPA to be effective, however, early diagnosis and rapid intervention are essential; patients targeted for tPA intervention must meet very specific inclusion and exclusion criteria to reduce the risk of hemorrhage (see accompanying table). In addition, careful analysis of the initial computed tomographic (CT) scan also appears to be critical in reducing the risk of intracranial hemorrhage. During the first 24 hours, patients given tPA cannot take anticoagulant and antiplatelet agents.

Inclusion and Exclusion Criteria for Thrombolysis of Acute Ischemic Stroke with tPA

Inclusion criteria

Age >18 years

Clinical diagnosis of ischemic stroke, with onset of symptoms within three hours of initiation of treatment

CT (noncontrast) without evidence of hemorrhage

Exclusion criteria

Historic

Stroke or head trauma in previous three months

History of intracranial hemorrhage that may increase risk of recurrent hemorrhage

Major surgery or other serious trauma in previous 14 days

Gastrointestinal or genitourinary bleeding in previous 21 days

Arterial puncture at a noncompressible site in previous seven days

Lumbar puncture in previous seven days

Pregnant or lactating woman

Clinical

Rapidly improving stroke symptoms

Seizure at onset of stroke

Symptoms suggestive of subarachnoid hemorrhage, even if CT is normal

Persistent systolic blood pressure >185 or diastolic blood pressure >110 mm Hg, or requiring aggressive therapy to control blood pressure

Clinical presentation consistent with acute myocardial infarction or post-myocardial infarction pericarditis requires cardiologic evaluation before treatment

Radiographic

CT with evidence of hemorrhage

CT with evidence of hypodensity and/or effacement of cerebral sulci in more than one third of middle cerebral artery territory

Laboratory

Glucose <50 or >400 mg per dL (<2.7 or >22.2 mmol per L)

Platelets <100,000 per mm3 (100,000 × 109 per L)

Warfarin therapy with a prothrombin time >15 seconds

Heparin therapy within 48 hours, and elevated partial thromboplastin time


tPA = tissue plasminogen activator; CT = computed tomography.

Reprinted with permission from Kasner SE, Grotta JC. Emergency identification and treatment of acute ischemic stroke. Ann Emerg Med 1997;30:644.

Inclusion and Exclusion Criteria for Thrombolysis of Acute Ischemic Stroke with tPA

View Table

Inclusion and Exclusion Criteria for Thrombolysis of Acute Ischemic Stroke with tPA

Inclusion criteria

Age >18 years

Clinical diagnosis of ischemic stroke, with onset of symptoms within three hours of initiation of treatment

CT (noncontrast) without evidence of hemorrhage

Exclusion criteria

Historic

Stroke or head trauma in previous three months

History of intracranial hemorrhage that may increase risk of recurrent hemorrhage

Major surgery or other serious trauma in previous 14 days

Gastrointestinal or genitourinary bleeding in previous 21 days

Arterial puncture at a noncompressible site in previous seven days

Lumbar puncture in previous seven days

Pregnant or lactating woman

Clinical

Rapidly improving stroke symptoms

Seizure at onset of stroke

Symptoms suggestive of subarachnoid hemorrhage, even if CT is normal

Persistent systolic blood pressure >185 or diastolic blood pressure >110 mm Hg, or requiring aggressive therapy to control blood pressure

Clinical presentation consistent with acute myocardial infarction or post-myocardial infarction pericarditis requires cardiologic evaluation before treatment

Radiographic

CT with evidence of hemorrhage

CT with evidence of hypodensity and/or effacement of cerebral sulci in more than one third of middle cerebral artery territory

Laboratory

Glucose <50 or >400 mg per dL (<2.7 or >22.2 mmol per L)

Platelets <100,000 per mm3 (100,000 × 109 per L)

Warfarin therapy with a prothrombin time >15 seconds

Heparin therapy within 48 hours, and elevated partial thromboplastin time


tPA = tissue plasminogen activator; CT = computed tomography.

Reprinted with permission from Kasner SE, Grotta JC. Emergency identification and treatment of acute ischemic stroke. Ann Emerg Med 1997;30:644.

Delays in recognition and treatment can be summarized by using the four D's: door (time until treatment), data (obtaining an electrocardiogram), decision (choice of therapy with thrombolysis) and drug (choice of agent). Education among health care providers at all levels and among the public as well is needed to expedite stroke treatment. Within the hospital, the use of a “stroke team” composed of neurologists, emergency physicians and nurses, along with radiologists and pharmacists, is appropriate to streamline diagnostic testing and emergency care of patients with signs and symptoms of stroke. If the criteria for thrombolysis are met, tPA infusion should be initiated in the emergency department, and the patient should be monitored closely for 24 hours.

The authors conclude that time is the most critical element in the successful treatment of an acute ischemic stroke. Since neural tissue is extremely sensitive to ischemic injury, thrombolysis with tPA should occur within three hours of the onset of symptoms if the patient meets the criteria for this therapy. Care of acute stroke must parallel that of acute myocardial infarction in ensuring early diagnosis and rapid intervention. A door-to-drug interval of 60 minutes is recommended as part of successful management.

Kasner SE, Grotta JC. Emergency identification and treatment of acute ischemic stroke. Ann Emerg Med. 1997 November;30:642–53.



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