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

OBJECTIVE: Urokinase has been conventionally used for intraarterial thrombo lysis in acute ischemic stroke. Recently, due to the withdrawal of urokinas e from the market, attention has been focused on recombinant tissue plasmin ogen activator (r-tPA) for intraarterial administration. Data is limited re garding the intraarterial dose, efficacy, and safety profile of this agent. METHODS: We prospectively studied 8 consecutive patients with acute ischemi c stroke who were referred for intraarterial lysis. Each patient was consid ered by the treating neurologist to be a poor candidate for intravenous the rapy. We administered a maximum total dose of 40 mg of r-tPA intraarteriall y via superselective catheterization. Angiograms were obtained after each 1 0 mg of r-tPA, and responses were graded using modified Thrombolysis in Myo cardial Infarction (TIMI) criteria for perfusion and degree of thrombus. RESULTS: Initial National Institutes of Health Stroke Scale (NIHSS) scores ranged from 16 to 21. Intervals from presentation to treatment initiation r anged from 1 to 8 hours. After administration of r-tPA, neurological improv ement (decrease in NIHSS score greater than or equal to 2) was observed in 4 patients. Mean perfusion grade improved from a pretreatment score of 0 wi th 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 degr ee 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 m g, and 1.4 +/- 1.5 after 40 mg. Asymptomatic intraparenchymal hemorrhage wa s observed on CT scan in 2 patients at 24 hours. CONCLUSION: Our study suggests that intraarterial r-tPA in doses up to 40 m g is relatively safe. The dose appears to facilitate the recanalization pro cess by lysis of local thrombus and improvement in distal flow.