Do not substitute: IV thrombolytic selection errors in acute stroke.

Do Not Substitute: IV Thrombolytic Selection Errors in Acute Stroke To the Editor: Activase (alteplase), commonly referred to as tPA, is a tissue-type plasminogen activator approved for treatment of ischemic stroke when given within 3 hours of symptom onset. Of the 6 thrombolytic drugs licensed for any use in the United States, Retaplase (reteplase), and TNKase (tenecteplase) share this mechanism of action. We have followed all stroke patients treated with intravenous thromblytics in our 4-hospital group since 1996 as part of an investigation into the community use of alteplase. Data are currently available for over 130 patients. We report 2 recent cases in which retevase was documented as substituted, a problem not previously reported in the literature or seen in our database prior to August 2000. Patient 1 was a 56-year-old man with a sudden left hemiparesis and hemisensory deficit who qualified for intravenous thrombolysis after cranial CT imaging. Following consent, orders were written for “tPA 9 mg IV over 1 to 2 minutes, 81 mg then over 1 hour. Total dose 90 mg.” The patient received a 9-U bolus of reteplase. The patient was notified of the error and admitted to the ICU per protocol. He was discharged 3 days later, ambulatory with 4/5 strength and normal sensation. Patient 2 was a 74-year-old man who also had an abrupt onset of left hemiparesis with sensory loss and a right gaze preference. CT demonstrated a hyperdense right middle cerebral artery sign. The only thrombolytic stocked in the involved emergency department was retevase. Nursing notes indicated “faxed tPA (order) to (inpatient) pharmacy” followed by “retavase 9 mg IVP given, retavase 81 mg to run in 60 minutes.” On review, the patient indeed received alteplase. Casual usage of the term “tPA” in thrombolytic therapy for acute myocardial infarction may have little consequence in the treatment outcome—each of the 6 drugs are approved for this use—assuming correct patient selection and dosing. Substitution in patients with acute stroke, however, may have serious consequences in terms of safety or efficacy, as only alteplase has approval in this setting. Adding to the confusion is the frequent usage of the terms “tPA,” “TPA,” and “rt-PA” in the stroke literature when referring specifically to treatment with alteplase, including the original efficacy trials published in the New England Journal of Medicine.1 Potential explanations for the sudden development of treatment errors after 4 years of usage include inappropriate utilization of the generic term “tPA” with an expanding number of agents using this mechanism; inadequate physician and staff knowledge of, and experience with, the increasing number of thrombolytics; the use of computerized medication dispensing systems (eg, Omnicell, Pixis), which do not recognize the term “tPA” or “rtPA”; similarities in the naming of thrombolytic agents; alterations in hospital formularies on a frequent basis; stocking of a single thrombolytic in the emergency department for cardiac usage; and a lack of understanding of the nonequivalence of cardiac thrombolytic agents and dosing in the treatment of stroke. Local corrective actions have included the revision of stroke treatment protocols to minimize the chance of substitution, reprogramming of drug dispensing machines, and increased staff education on thrombolytic agent differences. Heightened caution is advised for the proper selection of thrombolytic agents in patients with acute stroke.