TPA use requires caution, close monitoring
Critical restrictions limit use severely
Using extreme caution when administering and monitoring intravenous thrombolysis with recombinant tissue-type plasminogen activator (TPA) is crucial. You and your staff should be aware of the specific restrictions that exist as to TPA’s use.
Time of onset is critical. The window of opportunity is narrow. In addition, you can’t premedicate a patient with heparin or aspirin as you would for a myocardial infarction.
Time is brain’: The 3-hour window
The Chicago-based American Heart Association (AHA) guideline mandates administration of intravenous TPA for ischemic stroke in a dose of 0.9 mg/kg up to a maximum of 90 mg (10% of the dose in a bolus and the remainder infused over one hour) given within three hours of onset of stroke.1 The drug’s benefits persist over three months.
The administration of streptokinase (Streptase) is not recommended. Virtually no difference in outcome was demonstrated in an AHA study on the agent, but an excess of hematomas occurred in the treated group 13.2% as compared to 3% in the placebo group.
TPA, marketed by Genentech as Activase, is warned against in the guideline unless a diagnosis is established by a physician with expertise in stroke diagnosis as well as a CT scan. If the CT demonstrates early changes of a recent major infarction, such as sulcal effacement, mass effect, edema, or possible hemorrhage, thrombolytic therapy should be avoided.
Institutions have varying policies regarding who administers the drug. An internist at Shenandoah Memorial Hospital in Woodstock, VA, told an AMA audience recently that primary care physicians should become more comfortable with administering TPA and take responsibility for doing so. He said many physicians are afraid to do so outside the presence of a neurologist. He urged caution, of course, because giving the drug carries a 6% risk of intracranial hemorrhage.
Thrombolytic therapy is contraindicated
Thrombolytic therapy is also contraindicated unless emergent ancillary care and facilities to handle bleeding complications are available.
The therapy is cautioned in persons with severe stroke (NIH stroke scale score greater than 22) and not recommended for patients using oral anticoagulants such as warfarin sodium (Coumadin). In addition, the therapy is contraindicated in patients who have/had:
• another stroke or serious head injury in the previous three months;
• major surgery within the preceding 14 days;
• pretreatment systolic blood pressure greater than 185 mm Hg or diastolic blood pressure greater than 110 mm Hg;
• rapidly improving neurological signs;
• prothrombin time greater than 15 seconds (INR greater than 1.7);
• platelet count less than 100,000/mm3;
• isolated, mild neurological deficits, such as ataxia alone, sensory loss alone, dysarthria alone, or minimal weakness;
• a prior intracranial hemorrhage;
• blood glucose less than 50 mg/dL or greater than 400 mg/dL;
• a seizure at stroke onset;
• GI or urinary bleeding within the preceding 21 days;
• a recent MI.
ICU care is necessary during the administration of TPA and over the ensuing 24 hours, including close observation, frequent neurological assessments, and cardiovascular monitoring. Management of arterial blood pressure is critical. High blood pressure might predispose the patient to bleeding; hypotension may worsen ischemic symptoms. Restrict central venous access and arterial punctures. Avoid placing an indwelling bladder catheter during drug infusion and for 30 minutes after infusion. Avoid placing a nasogastric tube during first 24 hours after treatment.
Patients receiving TPA should not be given aspirin, heparin, warfarin, ticlopidine HCl (Ticlid), or other antithrombotic or antiplatelet-aggregating drugs for 24 hours.
Benefits somewhat restricted
Patients with extensive neurologic deficits and occlusion of the proximal middle cerebral artery may be less likely to benefit from intravenous thrombolysis. Administration of the drug can be complicated by site bleeding. Informed consent should be obtained before treatment is initiated.
Reference
1. Adams HP, Brott TG, Furlan AJ, et al, for the Stoke Council, American Heart Association: Guidelines for thrombolytic therapy for acute stroke. A supplement to the guidelines for the management of patients with acute ischemic stroke. Circulation. 1996; 94:1,167-1,174.
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