Intravenous thrombolysis, for

TABLE 3.1 Large Randomized Controlled Trials of Intravenous Thrombolysis for Acute Ischemic Stroke. 

Keris V, Rudnicka S, Vorona V, Enina G, Tilgale B, Fricbergs J. Combined intraarterial/ intravenous thrombolysis for acute ischemic stroke. Am JNeuroradiol 2001 22 352-358. 

Grond, M., et al.. Early intravenous thrombolysis for acute ischemic stroke in a community-based approach. Stroke,... 

Rammos SK, Neils DM, Fraser K, Klopfenstein JD. Anterior communicating artery aneurysm rupture after intravenous thrombolysis for acute middle cerebral artery thromboembolism case report. Neurosurgery June 2012 70(6) 1603-7. 

These studies raise the possibility that, one day, imaging-based treatment protocols may allow for intravenous thrombolysis in patients well outside of the now-accepted 3-hour window, provided they demonstrate substantial diffusion-perfusion mismatch. Such protocols could allow for treatment of a vastly larger number of patients than are currently treated. It has been estimated that only 1-7% of acute stroke patients currently receive thrombolytic medication, and that, in up to 95% of cases, they are ineligible because they present outside of the 3-hour time window. As many as 80% of patients who present 6 hours after stroke onset may demonstrate a significant diffusion-perfusion mismatch. "... 

Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boy sen G, Bluhmki E, Hoxter G, Mahagne MH. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995 274 1017-1025. 

Kent DM, Selker HP, Ruthazer R, Bluhmki E, Hacke W. The Stroke-Thrombol3dic Predictive Instrument. A predictive instrument for intravenous thrombolysis in acute ischemic stroke. Stroke. 2006 37 2957-2962. 

Comparisons between the different intra-arterial thrombolysis trials and between intraarterial thrombolysis and intravenous thrombolysis is hampered by differences in methodology and type of thrombolytic therapy. In addition, within the intra-arterial thrombolysis trials, thrombolytic deUvery has varied between regional into a parent vessel of the thrombosed vessel, local into the affected artery and into the thrombus itself, or combinations of these methods. In addition, the infusion process has been variable, ranging from continuous to pulsed infusion. Some studies have allowed physical clot dispersion using the tip of the microcatheter while this was prohibited in others, for instance in the PROACT trials. 

A 70-year-old woman was treated with intravenous alteplase for thrombolysis in acute ischemic stroke and 30 minutes later had acute sinus tachycardia and hypotension, followed by cyanosis and loss of consciousness... 

Zabel M, Hohnloser SH, Koster W, Prinz M, Kasper W, Just H, et ai. Analysis of creatine kinase, CK-2, myoglobin, and troponin T time-activity curves for early assessment of coronary artery reperfusion after intravenous thrombolysis. Circulation 1993 87 1542-50. 

Lee, KH., et al.. Usefulness of triphasic perfusion computed tomography for intravenous thrombolysis with tissue-type plasminogen activator in acute ischemic stroke. Arch Neurol,... 

Support for the potential role of PWI in selecting patients for intravenous thrombolysis has come from several studies in which thrombolysis was found to be effective later than 4.5 h, if offered only to patients with a large-enough diffusion-perfusion mismatch. One such study required at least a 50% mismatch between lesions seen on DWI and TTP maps, and found that thrombolysis could be effective up to 6 h [74]. In the Desmoteplase In Acute Ischemic Stroke (DIAS) and Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS) trials, thrombolysis was effective in patients presenting 3-9 h after onset, if offered only to those with at least a 20% mismatch between lesions seen on DWI, and on pseudo-MTT maps that were created using the normalized first... 

Unfortunately, two subsequently performed clinical trials provided less encouraging results. One of these, the DIAS-2 trial [78], again used intravenous thrombolysis in patients who presented 3-9 h after onset and had evidence of sufficient penumbra in acute-stage imaging. However DIAS-2 failed to show a benefit of thrombolysis. The imaging criteria used for this study were different from those in the original DIAS study. The authors did not specify the perfusion measurement that was used to measure the putative penumbra, and they allowed some sites to use perfusion measurements (obtained by CT rather than MR) to define both the core and the penumbra. 

Expanding the Time Window for Intravenous Thrombolysis Patient Selection Based on Multimodal Imaging... 

Acute ischemic stroke is treatable, and our ability to treat patients with ischemic stroke continues to improve. Since the publication of the first edition of this book, important changes in stroke patient management have occurred, and many are reflected in these pages. Perhaps the most important has been the widening of the time window for both intravenous thrombolysis as well as endovascular arterial recanalization treatments. This change in the expansion of the time window has major implications because it could dramatically increase the number of potential patients for treatment. Further expansion of the time window is possible with the likelihood that imaging will provide the necessary information for identifying suitable, individual patients. 

Three influential studies explore thrombolysis followed by obligatory coronary intervention compared with thrombolysis alone. These results diminished enthusiasm for a combined approach. A primary objective of one component of the TIMI II trial (TTMI Ha) was to determine whether early invasive management after acute STEMI would improve outcome (12). Patients eligible for enrollment in TTMI n were those with symptoms of less than 4 hours in duration and electrocardiographic manifestations of acute STEMI. All patients were treated with intravenous recombinant t-PA. In addition to t-PA, patients were treated with contemporary conjunctive and adjunctive therapy that included aspirin, unfractionated heparin, and intravenous hdocaine for a minimum of 24 hours. Within 1 hour after onset of infusion of t-PA, patients were given a bolus of 5000 units of unfractionated heparin in addition to a continuous infusion of 10(X) units per dose to induce a 1.5- to 2-fold... 

Thiemann DR, Coresh J, Schulman SP, Gerstenblith G, Oetgen WJ, Powe NR. Lack of benefit for intravenous thrombolysis in patients with myocardial infarction who are older than 75 years. Circulation 2000 101 2239-2246. 

Stroke is the leading cause of major long-term disability in adults and the third leading cause of death in the United States. On average, a new stroke occurs every 45 seconds. Thrombolytic therapy with intravenous recombinant tissue-plasminogen activator (IV rt-PA) is the most effective treatment for acute ischemic stroke. In this chapter, we review the rationale for thrombolysis in acute ischemic stroke, clinical evidence supporting the use of thrombolytics, and the application of thrombolysis in practice. 

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