Intraarterial recombinant tissue plasminogen activator for ischemic stroke: an accelerating dosing regimen

Urokinase has been conventionally used for intraarterial thrombolysis in acute ischemic stroke. Recently, due to the withdrawal of urokinase from the market, attention has been focused on recombinant tissue plasminogen activator (r-tPA) for intraarterial administration. Data is limited regarding the intraarterial dose, efficacy, and safety profile of this agent.

We prospectively studied 8 consecutive patients with acute ischemic stroke who were referred for intraarterial lysis. Each patient was considered by the treating neurologist to be a poor candidate for intravenous therapy. We administered a maximum total dose of 40 mg of r-tPA intraarterially via superselective catheterization. Angiograms were obtained after each 10 mg of r-tPA, and responses were graded using modified Thrombolysis in Myocardial Infarction (TIMI) criteria for perfusion and degree of thrombus.

Initial National Institutes of Health Stroke Scale (NIHSS) scores ranged from 16 to 21. Intervals from presentation to treatment initiation ranged from 1 to 8 hours. After administration of r-tPA, neurological improvement (decrease in NIHSS score > or =2) was observed in 4 patients. Mean perfusion grade improved from a pretreatment score of 0 with increasing doses of r-tPA to 1.1 +/- 1.0 with 10 mg, 1.5 +/- 1.4 with 20 mg, 2.0 +/- 0.8 with 30 mg, and 2.7 +/- 1.0 with 40 mg. Mean thrombus degree decreased from a pretreatment score of 4 with increasing doses of r-tPA to 2.8 +/- 1.2 after 10 mg, 2.6 +/- 1.4 after 20 mg, 1.9 +/- 1.5 after 30 mg, and 1.4 +/- 1.5 after 40 mg. Asymptomatic intraparenchymal hemorrhage was observed on CT scan in 2 patients at 24 hours.

Our study suggests that intraarterial r-tPA in doses up to 40 mg is relatively safe. The dose appears to facilitate the recanalization process by lysis of local thrombus and improvement in distal flow.