A critical analysis of intra-arterial thrombolytic doses in acute ischemic stroke treatment

Background: Intra-arterial thrombolytics (IAT) such as Alteplase, Tenecteplase, and Reteplase are currently used in patients with acute ischemic stroke in varying doses. We evaluated the relationship of IA thrombolytic dose with angiographic recanalization, intracerebral hemorrhage (ICH) rates, and clinical outcomes at three comprehensive stroke centers. Methods: We stratified patients who underwent endovascular treatment into tertiles based on intra-arterial thrombolytic dose administered: lower tertile (range 1.5-5 mg), middle tertile (range 6-10 mg), and upper tertile (range 10.3-68.5 mg) of rt-PA equivalent. The rates of angiographic recanalization, ICH, and favorable clinical outcomes (discharge modified Rankin score [mRS] = 0-2) were ascertained and compared within the three tertiles. Logistic regression analyses were performed to determine the association between IA thrombolytic dosages and angiographic recanalization, ICH, and favorable clinical outcomes after adjusting for potential confounders. Results: A total of 197 patients were treated with IAT; mean age ±SD was 65.6 ± 16 years; 105 (53.3 %) were women. Ninety-one (46.2 %) patients received both IVT and IAT. IA rt-PA equivalent dose was not different between the patients with and without ICH [mean (mg) ± SD, 9.8 ± 6.1 versus 9.8 ± 9.5, p = 0.9]. We did not find any relation between increasing doses of IAT (from 2 to 69 mg rt-PA equivalent) and symptomatic or asymptomatic ICH: (p = 0.1630) and (p = 0.6702), respectively. Multivariate analysis demonstrated that IAT dose was not associated with ICH (OR 1.0, 95 % CI 0.97-1.07, p = 0.3919) or favorable outcome (OR, 1.00, 95 % CI 0.95-1.06, p = 0.7375). In a subset analysis of IVT patients, total doses ranged from 48.2 to 149 mg and were not associated with either symptomatic (p = 0.23) or asymptomatic (p = 0.24) ICHs. Conclusion: Our study demonstrates that IAT in doses up to 69 mg is safe without any evidence of dose-related ICHs even in those patients who had received IVT.