Original article Intravenous thrombolysis in the emergency department for the treatment of acute ischaemic stroke A Semplicini,1 V Benetton,1 L Macchini,1 A Realdi,1 R Manara,2 C Carollo,2 E Parotto,1 V Mascagna,1 M Leoni,1 L A Cal`o,1 A C Pessina,1 F Tosato3 1 Department of Clinical and Experimental Medicine, University of Padua Medical School and Azienda Ospedaliera, Padua, Italy; 2 Department of Neurological Sciences, University of Padua Medical School and Azienda Ospedaliera, Padua, Italy; 3 Emergency Department, University of Padua Medical School and Azienda Ospedaliera, Padua, Italy Correspondence to: Professor A Semplicini, Clinica Medica 4, Department of Clinical and Experimental Medicine, Policlinico Universitario, Via Giustiniani 2, I-35128 Padova, Italy; andrea.semplicini@ unipd.it Accepted 27 November 2007 This paper is freely available online under the BMJ Journals unlocked scheme, see http:// emj.bmj.com/info/unlocked.dtl Emerg Med J 2008;25:403–406. doi:10.1136/emj.2007.053033 ABSTRACT Background and aims: Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (rt- PA) improves outcome in patients with ischaemic stroke treated within 3 h of symptom onset, but its extended implementation is limited. A pilot study was designed to verify whether evaluation of patients with acute ischaemic stroke and their treatment with intravenous rt-PA in the emergency department (ED), followed by transportation to a semi-intensive stroke care unit, offers a safe and effective organisational solution to provide intravenous thrombolysis to acute stroke patients when a stroke unit (SU) is not available. Methods: After checking for inclusion and exclusion criteria, ED doctors contacted the stroke team with a single page, located family members and urgently obtained computed tomography scan and laboratory tests. A stroke team investigator clinically assessed the patient, obtained written informed consent and super- vised intravenous rt-PA in the ED. After treatment, the patient was transferred to the SU for rehabilitation and treatment of complications, under supervision of the same stroke team investigator. Results: 52 patients were treated with intravenous rt-PA within 3 h of symptom onset. 20 patients (38%) improved neurologically after 24 h, the number increased to 30 (58%) after one week. At 3 months 22 patients had a favourable outcome (43%). The 3-month mortality rate was 12%. Symptomatic cerebral haemorrhage was observed in two patients (4%). Conclusions: Intravenous rt-PA administration in the ED is an effective organisational solution for acute ischaemic stroke when an SU is not established. Thrombolytic therapy with intravenous recombi- nant tissue plasminogen activator (rt-PA) has been shown to improve outcome in patients with ischaemic stroke treated within 3 h of symptom onset.1 In the United States, however, 69% of hospitals do not use thrombolysis at all and only 1% of stroke patients receive thrombolytics, mostly at hospitals with a high volume of stroke patients.2 This implies that only immediate referral of stroke patients to strategically placed, certified, high-volume stroke centres with continuously available, dedicated and sophisticated stroke teams, analogous to the manner in which trauma patients are routed to certified trauma centres, may increase the thrombolysis rate.2 Until recently, the extended use of thrombolytic therapy with intravenous rt-PA has been prevented in Europe by concerns about its safety profile, as it increases the risk of cerebral haemorrhage, and its efficacy in clinical practice where stroke units (SU) are not available. The SITS–MOST trial, aiming to define the risks of rt-PA administration to patients with acute ischaemic stroke within 3 h of symp- tom onset in experienced stroke centres in Europe, has shown a favourable risk–benefit ratio.3 It is still debated how to implement thrombolytic therapy, once its extended use has been approved. In fact, widespread experience is limited and the number of SU in most countries is small and unevenly distributed, so that transportation of the patient to the closest SU may delay treatment and may further reduce the number of candidate patients. In 2000, an SU was not established in our institution and intravenous rt-PA was not regis- tered for the treatment of stroke in Italy. Therefore, we designed a pilot clinical study to investigate how to implement intravenous throm- bolysis for the treatment of ischaemic stroke. The study assessed the safety and outcome of intrave- nous thrombolysis with rt-PA in the emergency department (ED), followed by transfer of patients to a semi-intensive SU for follow-up monitoring, further treatment and rehabilitation. METHODS Stroke team collaboration was established at the University Hospital of Padua, a large academic city hospital with more than 100 000 consultations per year in the ED. The aim of stroke team collabora- tion was to increase awareness about appropriate treatments of acute ischaemic stroke (ie, intrave- nous and intra-arterial thrombolysis, as well as endovascular procedures). In particular, its aim was to evaluate how to implement off-label intrave- nous thrombolysis with rt-PA in acute ischaemic stroke, before the institution of the SU and the formal approval of rt-PA in stroke patients by the European and local regulatory agencies. This pilot clinical trial was approved by the local Ethical Committee in 1999 and lasted from 1 January 2000 to 30 June 2007. The stroke team was composed of internists, neurologists, neuroradiologists, emergency doctors and anaesthetists. Its first task was to train the doctors of the ED about triage and the manage- ment of patients with acute stroke, so that any patient admitted to the ED with suspected ischaemic stroke was immediately triaged by ED doctors for indications for systemic thrombolysis. The inclusion/exclusion criteria for thrombolysis were those of the National Institute of 403