Bolus-Infusion Delays of Alteplase during Thrombolysis in Acute Ischaemic Stroke and Functional Outcome at 3 Months

Background. The efficacy of alteplase in acute ischaemic stroke (AIS) is highly time dependent. Hence, alteplase is administered as soon as possible with a bolus followed by an infusion. Delays between bolus and infusion may occur, but the extent of these delays and the impact on outcome are unclear. Aims. We investigated the extent of bolus-infusion delays and the relationship between delays and stroke outcome. Method. We reviewed medical records of 276 patients who received alteplase for AIS at our centre between April, 2008, and June, 2013. Complete demographic and clinical data including 3-month modified Rankin Score (mRS) from 229 patients were analysed comparing delays of 0–8 and >8 minutes. Results. Overall mean (SD) bolus-infusion delay was 9 (7) minutes. Baseline characteristics were similar apart from more severe strokes in delays >8 minutes. Three-month outcomes were not significantly different although delays >8 minutes had lower functional independence rate (mRS 0-1: 23.1% versus 28.1%; adjusted OR 1.2 (95% CI 0.6 to 2.4, )) and higher mortality rate (18% versus 11%, OR 1.0, 95% CI 0.6 to 1.7, ). Conclusions. In this single centre series, bolus-infusion delays of alteplase in AIS were common and no effect of bolus-infusion delays on independence and mortality was found. 1. Introduction Alteplase is licensed for use in acute ischaemic stroke (AIS). Its efficacy in improving stroke outcome depends on onset to treatment time (OTT) [1]. Alteplase has a short plasma half-life of about 4 minutes [2] and is administered at a dose of 0.9？mg/kg body weight with 10% of the total dose given as a bolus over 1-2 minutes and the remainder infused over an hour. This regimen has been demonstrated to achieve functional improvement with a low risk of intracranial haemorrhage [3]. None of the trials of alteplase in AIS reported the extent of bolus-infusion delays. Indeed, there are very limited data on the pharmacokinetic profile of alteplase as used in AIS [4, 5]. Considering the short half-life of alteplase, significant bolus-infusion delays may result in delayed or suboptimum steady state kinetics which could adversely influence outcome. We investigated the extent of bolus-infusion delays of alteplase in AIS in a single centre and its relationship with functional outcome at 3 months. 2. Materials and Methods We retrospectively reviewed medical records of patients treated with alteplase within 4.5？h after AIS at Newcastle upon Tyne Hospitals Trust from April 2008 to June 2013. Data on baseline demographics and relevant clinical parameters, functional