Identification of suspected stroke in the dispatch center of the Berlin Fire Brigade prompts the deployment of a CT-equipped ambulance. If ischemic stroke is confirmed and contraindications are excluded prehospital thrombolysis is applied.
In acute ischemic stroke, time from symptom onset to intervention is a decisive prognostic factor. In order to reduce this time, prehospital thrombolysis at the emergency site would be preferable. However, apart from neurological expertise and laboratory investigations a computed tomography (CT) scan is necessary to exclude hemorrhagic stroke prior to thrombolysis. Therefore, a specialized ambulance equipped with a CT scanner and point-of-care laboratory was designed and constructed. Further, a new stroke identifying interview algorithm was developed and implemented in the Berlin emergency medical services. Since February 2011 the identification of suspected stroke in the dispatch center of the Berlin Fire Brigade prompts the deployment of this ambulance, a stroke emergency mobile (STEMO). On arrival, a neurologist, experienced in stroke care and with additional training in emergency medicine, takes a neurological examination. If stroke is suspected a CT scan excludes intracranial hemorrhage. The CT-scans are telemetrically transmitted to the neuroradiologist on-call. If coagulation status of the patient is normal and patient's medical history reveals no contraindication, prehospital thrombolysis is applied according to current guidelines (intravenous recombinant tissue plasminogen activator, iv rtPA, alteplase, Actilyse).
Thereafter patients are transported to the nearest hospital with a certified stroke unit for further treatment and assessment of strokeaetiology. After a pilot-phase, weeks were randomized into blocks either with or without STEMO care. Primary end-point of this study is time from alarm to the initiation of thrombolysis. We hypothesized that alarm-to-treatment time can be reduced by at least 20 min compared to regular care.
Thrombolysis with intravenous recombinant tissue Plasminogen Activator (rtPA) is the only proven effective treatment in acute ischemic stroke. The benefits of thrombolysis are time-dependent. Efficacy of thrombolytic therapy for ischemic stroke decreases with time elapsed from symptom onset1. Therefore, delays until initiation of treatment must be avoided. However, there are prehospital and in-hospital reasons for delays in treatment initiation. Patients' decision time to call emergency services and the time from emergency call to arrival at the hospital are factors in the prehospital delay. In hospital, reductions of both the time to CT scanning and of the time between CT scan and start of thrombolysis remain challenging2. Stroke awareness campaigns shorten patient related times to emergency call3, but effects are only temporary and require repetition of such campaigns. While there are successful examples of reducing in-hospital delay 4,5 many centers struggle to remain within the required 60 min from door to needle. One way to avoid these delays may be a start of specific stroke treatment at the emergency site, i.e. prehospital thrombolysis. Until recently, several requirements made this unfeasible. First, only physicians experienced in stroke care are qualified to make acute treatment decisions. Second, computed tomography (CT) is necessary to rule out intracranial hemorrhage. Third, laboratory tests should be available to exclude coagulation disorders6. In order to overcome these challenges, a stroke emergency mobile (STEMO) was constructed. This special ambulance is equipped with a CT scanner, a point-of-care laboratory and an infrastructure for teleradiological support7. It is operated by a highly specialized crew consisting of experienced neurologists, paramedics of the Berlin Fire Brigade, and radiology technicians8. To meet the legal requirements and the requirements of the Berlin Medical Board, each neurologist involved completed an additional training in emergency medicine. Radiology technicians completed a three month formal training in emergency care9. STEMO has been integrated in public emergency medical services (EMS) provided by the Berlin Fire Brigade. For the identification of eligible patients with suspected stroke during the emergency call, a special interview algorithm was developed and integrated at the dispatcher level10. During a three months pilot-study, we demonstrated safety and feasibility11. Our colleagues from Homburg, Germany, recently published their experience with the first 12 prehospital thrombolysis in the Saarland State12. We believe that prehospital stroke care using STEMO can reduce the alarm-to-needle time compared to regular care ultimately leading to improved patients care. However, prior to implementation final results of sufficiently powered studies need to confirm safety and efficacy of this approach. Here we present the methods used in the "prehospital acute neurological therapy and optimization of medical care in stroke patients" study (PHANTOM-S).
Prehospital thrombolysis may be able to revolutionize acute specific stroke treatment. However, it is a cost and resource consuming way of treatment delivery. In general, a 'stay-and-play' rather than a 'load-and-go' approach needs to be justified by specific characteristics of the emergency at hand. Ischemic stroke has distinctive features that warrant a 'treat-and-run' compromise: The benefits of acute stroke treatment are enormously time dependent. During an ischemic stroke approximately 2,000,000 neurons die per minute14. Intravenous treatment with rtPA enhances the chances of reperfusion and favorable functional outcome in stroke patients15. Treatment should be started as soon as possible. By now, it is the only evidence-based, effective and approved treatment for acute ischemic stroke. Associated with the risk of severe bleeding, the exclusion of intracranial bleeds and other contraindications is mandatory prior to thrombolysis. STEMO is set up to prove that this specific treatment can be safely administered in a prehospital setting and actually safes time compared to regular care8,11. First results from 12 prehospital thrombolyses in the Saarland State, Germany, seem promising in this respect12. In this study, Walter and colleagues reported that after randomized weeks between November, 2008, and July, 2011 and an interim analysis at 100 of 200 planned patients (53 in the prehospital setting, 47 in the control group), the median time from alarm to therapy decision (primary end-point) was substantially reduced in the 12 cases of prehospital thrombolysis: 35 min (IQR 31-39) versus 76 min, p<0.0001; median difference 41 min (95% CI 36-48 min). Overall, the additional costs have to be weighed against benefits that patients may experience. For this, the final results of the ongoing PHANTOM-S will be crucial. In this prospective study (http://clinicaltrials.gov/ct2/show/ NCT01382862), weeks with and without STEMO on duty are randomized until 228 patients have received iv rtPA in both treatment arms. Primary end-point of the study is time from alarm to thrombolysis. Secondary end-points include modified Rankin Scale score after three months, symptomatic intracranial hemorrhage, mortality and cost effectiveness. Results of this study will help decision makers whether to implement prehospital thrombolysis of acute ischemic stroke patients with specialized ambulances in their emergency systems. Site specific adaptations may be necessary. For instance, in regions with a shortage of neurologists telemedicine may provide the expertise to the emergency physician on board. Similarly, the results of the PHANTOM-S study may help to identify regions with the most likely benefit for patients and cost effectiveness for authorities. So far, it is not known whether prehospital thrombolysis is the most appropriate approach in mega-cities, urban, or rural settings16. Taken together, prehospital thrombolysis seems to be a logical step when the need of shortening time to treatment is taken seriously. Only a sufficiently powered study may provide the evidence of actual benefit to stroke patients.
The authors have nothing to disclose.
We wish to acknowledge all of the funding organizations, the "Technology Foundation Berlin" (TSB) via the "Zukunftsfonds Berlin", the Federal Ministry of Education and Research via the grant CSB (01 EO 0801), the Volkswagen Foundation (Lichtenberg program to Matthias Endres), the EU (EuStroke, ARISE) and the German Research Foundation (NeuroCure, SFB-TR 43).
Drug | |||
Alteplase (rtPA) | Boehringer-Ingelheim | Licensed drug | |
Table 1. Alteplase. Alteplase (tissue-Plasminogen Activator) is the only licensed drug for acute ischemic stroke that has proven effectiveness within 4.5 hr of symptom onset in randomized controlled trials. | |||
Device | |||
ABX micros 60 | Horiba Medical | Point-of-care laboratory | |
CereTom | NeuroLogica | CT-Scanner | |
CoaguChek XSPlus | Roche | Handheld blood analyzer | |
EBA 20 | HettichLab | centrifuge | |
FastPack System | Qualigen | Point-of-care immunoassay | |
i-STAT | Abbot | Handheld blood analyzer | |
OptiStat | Siemens | Contrast agent delivery system | |
Pilot A2 | Fresenius | Infusion pump | |
TGL 12.250 4 x 2 BL | MAN | Vehicle chassis | |
Van body | Fahrtec Systeme GmbH | Custom-built | |
Vimed COMM | MEYTEC GmbH | Video communication system | |
Vimed GATEWAY | MEYTEC GmbH | Network solution | |
Vimed STEMO-DOC | MEYTEC GmbH | Documentation software | |
Vimed TELEMED | MEYTEC GmbH | Equipment for telemedicine | |
Vimed WEB-ENTRY | MEYTEC GmbH | Teleradiology | |
Table 2. Table of specific equipment. The software solution used in the ambulance was developed by a partner of the STEMO-consortium, MEYTEC GmbH, Germany. MEYTEC designed and implemented the overall technical solution. The entire system can be obtained from the partner MEYTEC under the name VIMED STEMO. |