Carolin Waldschmidt

Effect of the Use of Ambulance-Based Thrombolysis on Time to Thrombolysis in Acute Ischemic Stroke: A Randomized Clinical Trial

IMPORTANCE Time to thrombolysis is crucial for outcome in acute ischemic stroke. OBJECTIVE To determine if starting thrombolysis in a specialized ambulance reduces delays. DESIGN, SETTING, AND PARTICIPANTS In the Prehospital Acute Neurological Treatment and Optimization of Medical care in Stroke Study (PHANTOM-S), conducted in Berlin, Germany, we randomly assigned weeks with and without availability of the Stroke Emergency Mobile (STEMO) from May 1, 2011, to January 31, 2013. Berlin has an established stroke care infrastructure with 14 stroke units. We included 6182 adult patients (STEMO weeks: 44.3% male, mean [SD] age, 73.9 [15.0] y; control weeks: 45.2% male, mean [SD] age, 74.3 [14.9] y) for whom a stroke dispatch was activated. INTERVENTIONS The intervention comprised an ambulance (STEMO) equipped with a CT scanner, point-of-care laboratory, and telemedicine connection; a stroke identification algorithm at dispatcher level; and a prehospital stroke team. Thrombolysis was started before transport to hospital if ischemic stroke was confirmed and contraindications excluded. MAIN OUTCOMES AND MEASURES Primary outcome was alarm-to-thrombolysis time. Secondary outcomes included thrombolysis rate, secondary intracerebral hemorrhage after thrombolysis, and 7-day mortality. RESULTS Time reduction was assessed in all patients with a stroke dispatch from the entire catchment area in STEMO weeks (3213 patients) vs control weeks (2969 patients) and in patients in whom STEMO was available and deployed (1804 patients) vs control weeks (2969 patients). Compared with thrombolysis during control weeks, there was a reduction of 15 minutes (95% CI, 11-19) in alarm-to-treatment times in the catchment area during STEMO weeks (76.3 min; 95% CI, 73.2-79.3 vs 61.4 min; 95% CI, 58.7-64.0; P < .001). Among patients for whom STEMO was deployed, mean alarm-to-treatment time (51.8 min; 95% CI, 49.0-54.6) was shorter by 25 minutes (95% CI, 20-29; P < .001) than during control weeks. Thrombolysis rates in ischemic stroke were 29% (310/1070) during STEMO weeks and 33% (200/614) after STEMO deployment vs 21% (220/1041) during control weeks (differences, 8%; 95% CI, 4%-12%; P < .001, and 12%, 95% CI, 7%-16%; P < .001, respectively). STEMO deployment incurred no increased risk for intracerebral hemorrhage (STEMO deployment: 7/200; conventional care: 22/323; adjusted odds ratio [OR], 0.42, 95% CI, 0.18-1.03; P = .06) or 7-day mortality (9/199 vs 15/323; adjusted OR, 0.76; 95% CI, 0.31-1.82; P = .53). CONCLUSIONS AND RELEVANCE Compared with usual care, the use of ambulance-based thrombolysis resulted in decreased time to treatment without an increase in adverse events. Further studies are needed to assess the effects on clinical outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01382862.

Prehospital thrombolysis in acute stroke Results of the PHANTOM-S pilot study

Objective: Beneficial effects of IV tissue plasminogen activator (tPA) in acute ischemic stroke are strongly time-dependent. In the Pre-Hospital Acute Neurological Treatment and Optimization of Medical care in Stroke (PHANTOM-S) study, we undertook stroke treatment using a specialized ambulance, the stroke emergency mobile unit (STEMO), to shorten call-to-treatment time. Methods: The ambulance was staffed with a neurologist, paramedic, and radiographer and equipped with a CT scanner, point-of-care laboratory, and a teleradiology system. It was deployed by the dispatch center whenever a specific emergency call algorithm indicated an acute stroke situation. Study-specific procedures were restricted to patients able to give informed consent. We report feasibility, safety, and duration of procedures regarding prehospital tPA administration. Results: From February 8 to April 30, 2011, 152 subjects were treated in STEMO. Informed consent was given by 77 patients. Forty-five (58%) had an acute ischemic stroke and 23 (51%) of these patients received tPA. The mean call-to-needle time was 62 minutes compared with 98 minutes in 50 consecutive patients treated in 2010. Two (9%) of the tPA-treated patients had a symptomatic intracranial hemorrhage and 1 of these patients (4%) died in hospital. Technical failures encountered were 1 CT dysfunction and 2 delayed CT image transmissions. Conclusions: The data suggest that prehospital stroke care in STEMO is feasible. No safety concerns have been raised so far. This new approach using prehospital tPA may be effective in reducing call-to-needle times, but this is currently being scrutinized in a prospective controlled study.

Telestroke Ambulances in Prehospital Stroke Management Concept and Pilot Feasibility Study

Background and Purpose— Pre- and intrahospital time delays are major concerns in acute stroke care. Telemedicine-equipped ambulances may improve time management and identify patients with stroke eligible for thrombolysis by an early prehospital stroke diagnosis. The aims of this study were (1) to develop a telestroke ambulance prototype; (2) to test the reliability of stroke severity assessment; and (3) to evaluate its feasibility in the prehospital emergency setting. Methods— Mobil, real-time audio–video streaming telemedicine devices were implemented into advanced life support ambulances. Feasibility of telestroke ambulances and reliability of the National Institutes of Health Stroke Scale assessment were tested using current wireless cellular communication technology (third generation) in a prehospital stroke scenario. Two stroke actors were trained in simulation of differing right and left middle cerebral artery stroke syndromes. National Institutes of Health Stroke Scale assessment was performed by a hospital-based stroke physician by telemedicine, by an emergency physician guided by telemedicine, and “a posteriori” on the basis of video documentation. Results— In 18 of 30 scenarios, National Institutes of Health Stroke Scale assessment could not be performed due to absence or loss of audio–video signal. In the remaining 12 completed scenarios, interrater agreement of National Institutes of Health Stroke Scale examination between ambulance and hospital and ambulance and “a posteriori” video evaluation was moderate to good with weighted &kgr; values of 0.69 (95% CI, 0.51–0.87) and 0.79 (95% CI, 0.59–0.98), respectively. Conclusion— Prehospital telestroke examination was not at an acceptable level for clinical use, at least on the basis of the used technology. Further technical development is needed before telestroke is applicable for prehospital stroke management during patient transport.

PHANTOM-S: the prehospital acute neurological therapy and optimization of medical care in stroke patients – study

Rationale Time from symptom onset to treatment is closely associated with the effectiveness of intravenous thrombolysis in acute ischemic stroke patients. Hospitals are encouraged to take every effort to shorten delay of treatment. Despite combined efforts to streamline procedures in hospitals to provide treatment as soon as possible, most patients receive tissue plasminogen activator with considerable delay and very few of them within 90 mins. Germany has an internationally acknowledged prehospital emergency care system with specially trained doctors on ambulances. We developed an ambulance equipped with a Computed Tomography (CT) scanner, point-of-care laboratory, teleradiological support, and an emergency-trained neurologist on board. In the Pre-Hospital Acute Neurological Therapy and Optimization of Medical care in Stroke Patients study, we aim at a reduction of the current alarm-to-needle time by prehospital use of tissue plasminogen activator in an ambulance. Aims We hypothesized that compared with regular care, we will reduce alarm-to-needle time by a minimum of 20 mins by implementation of the stroke emergency mobile unit. Design Prospective study comparing randomly allocated periods with and without stroke emergency mobile unit availability. Study Outcomes Primary end point of the study is alarm-to-needle time. Secondary outcomes include thrombolysis treatment rates, modified Rankin scale after three-months, and alarm-to-imaging or alarm-to-laboratory time; safety aspects to be evaluated are mortality and rates of (symptomatic) intracerebral hemorrhage.

Functional outcomes of pre-hospital thrombolysis in a mobile stroke treatment unit compared with conventional care: an observational registry study

BACKGROUND Specialised CT-equipped mobile stroke treatment units shorten time to intravenous thrombolysis in acute ischaemic stroke by starting treatment before hospital admission; however, direct effects of pre-hospital thrombolysis on clinical outcomes have not been shown. We aimed to compare 3-month functional outcomes after intravenous thrombolysis in patients with acute ischaemic who had received emergency mobile care or and conventional care. METHODS In this observational registry study, patients with ischaemic stroke received intravenous thrombolysis (alteplase) either within a stroke emergency mobile (STEMO) vehicle (pre-hospital care covering 1·3 million inhabitants of Berlin) or within conventional care (normal ambulances and in-hospital care at the Charité Campus Benjamin Franklin in Berlin). Patient data on treatment, outcome, and demographics were documented in STEMO (pre-hospital) or conventional care (in-hospital) registries. The primary outcome was the proportion of patients who had lived at home without assistance before stroke and had a 3-month modified Rankin Scale (mRS) score of 1 or lower. Our multivariable logistic regression was adjusted for demographics, comorbidities, and stroke severity. This study is registered with ClinicalTrials.gov, number NCT02358772. FINDINGS Between Feb 5, 2011, and March 5, 2015, 427 patients were treated within the STEMO vehicle and their data were entered into a pre-hospital registry. 505 patients received conventional care and their data were entered into an in-hospital thrombolysis registry. Of these, 305 patients in the STEMO group and 353 in the conventional care group met inclusion criteria and were included in the analysis. 161 (53%) patients in the STEMO group versus 166 (47%) in the conventional care group had an mRS score of 1 or lower (p=0·14). Compared with conventional care, adjusted odds ratios (ORs) for STEMO care for the primary outcome (OR 1·40, 95% CI 1·00-1·97; p=0·052) were not significant. Intracranial haemorrhage (p=0·27) and 7-day mortality (p=0·23) did not differ significantly between treatment groups. INTERPRETATION We found no significant difference between the proportion of patients with a mRS score of 1 or lower receiving STEMO care compared with conventional care. However, our results suggest that pre-hospital start of intravenous thrombolysis might lead to improved functional outcome in patients. This evidence requires substantiation in future large-scale trials. FUNDING Zukunftsfonds Berlin, the Technology Foundation Berlin with EU co-financing by the European Regional Development Fund via Investitionsbank Berlin, and the German Federal Ministry for Education and Research via the Center for Stroke Research Berlin.

Improved Prehospital Triage of Patients With Stroke in a Specialized Stroke Ambulance: Results of the Pre-Hospital Acute Neurological Therapy and Optimization of Medical Care in Stroke Study

Background and Purpose— Specialized management of patients with stroke is not available in all hospitals. We evaluated whether prehospital management in the Stroke Emergency Mobile (STEMO) improves the triage of patients with stroke. Methods— STEMO is an ambulance staffed with a specialized stroke team and equipped with a computed tomographic scanner and point-of-care laboratory. We compared the prehospital triage of patients with suspected stroke at dispatcher level who either received STEMO care or conventional care. We assessed transport destination in patients with different diagnoses. Status at hospital discharge was used as short-term outcome. Results— From May 2011 to January 2013, 1804 of 6182 (29%) patients received STEMO care and 4378 of 6182 (71%) patients conventional care. Two hundred forty-five of 2110 (11.6%) patients with cerebrovascular events were sent to hospitals without Stroke Unit in conventional care when compared with 48 of 866 (5.5%; P<0.01%) patients in STEMO care. In patients with ischemic stroke, STEMO care reduced transport to hospitals without Stroke Unit from 10.1% (151 of 1497) to 3.9% (24 of 610; P<0.01). The delivery rate of patients with intracranial hemorrhage to hospitals without neurosurgery department was 43.0% (65 of 151) in conventional care and 11.3% (7 of 62) in STEMO care (P<0.01). There was a slight trend toward higher rates of patients discharged home in neurological patients when cared by STEMO (63.5% versus 60.8%; P=0.096). Conclusions— The triage of patients with cerebrovascular events to specialized hospitals can be improved by STEMO ambulances. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01382862.

Copeptin Levels in Patients With Acute Ischemic Stroke and Stroke Mimics

Background and Purpose— Copeptin levels are increased in patients diagnosed with stroke and other vascular diseases. Copeptin elevation is associated with adverse outcome, predicts re-events in patients with transient ischemic attack and is used in ruling-out acute myocardial infarction. We evaluated whether copeptin can also be used as a diagnostic marker in the prehospital stroke setting. Methods— We prospectively examined patients with suspected stroke on the Stroke Emergency Mobile—an ambulance that is equipped with computed tomography and point-of-care laboratory. A blood sample was taken from patients immediately after arrival. We analyzed copeptin levels in patients with final hospital-based diagnosis of stroke or stroke mimics as well as in vascular or nonvascular patients. In addition, we examined the associations of symptom onset with copeptin levels and the prognostic value of copeptin in patients with stroke. Results— Blood samples of 561 patients were analyzed. No significant differences were seen neither between cerebrovascular (n=383) and other neurological (stroke mimic; n=90) patients (P=0.15) nor between vascular (n=391) and nonvascular patients (n=170; P=0.57). We could not detect a relationship between copeptin levels and time from onset to blood draw. Three-month survival status was available in 159 patients with ischemic stroke. Copeptin levels in nonsurviving patients (n=8: median [interquartile range], 27.4 [20.2–54.7] pmol/L) were significantly higher than in surviving patients (n=151: median [interquartile range], 11.7 [5.2–30.9] pmol/L; P=0.024). Conclusions— In the prehospital setting, copeptin is neither appropriate to discriminate between stroke and stroke mimic patients nor between vascular and nonvascular patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01382862. The Pre-Hospital Acute Neurological Therapy and Optimization of Medical Care in Stroke Patients study (PHANTOM-S) was registered (NCT01382862). This sub-study was observational and not registered separately, therefore.

Prehospital Thrombolysis: A Manual from Berlin

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 patients 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.

Glial Fibrillary Acidic Protein for Prehospital Diagnosis of Intracerebral Hemorrhage

Background: Both, acute ischemic stroke (AIS) and hemorrhage stroke (intracerebral hemorrhage, ICH) require early attention but different treatment strategies. Plasma glial fibrillary acidic protein (GFAP) levels were found to be elevated in ICH patients after they arrived in the hospital. Because treatment options differed, we sought to determine whether GFAP can be used to accurately differentiate between of AIS and ICH in the prehospital setting. Methods: We assessed acute stroke patients in the Stroke Emergency Mobile (STEMO). STEMO is a stroke ambulance staffed by a specialized team including a neurologist and equipped with a computed tomography scanner plus a point-of-care laboratory. The STEMO ambulance is integrated in the emergency medical system of Berlin, Germany. Following prehospital stroke diagnosis, blood was drawn and subsequently analysed using research assays from Roche diagnostics. The clinical accuracy of plasma GFAP was tested using a cut-off value of 0.29 ng/ml. Results: Blood samples of 74 patients were analysed. Twenty-five patients had ICH (mean age 69 ± 11 years, median National Institutes of Health Stroke Scale (NIHSS) 15) and 49 IS (mean age 75 ± 10 years, median NIHSS 6). Nine ICH (0 IS patients) had GFAP-levels above 0.29 ng/ml. The sensitivity and specificity of GFAP for differentiating between ICH and AIS were 36.0 and 100%. The sensitivity for ICH volume >15 ml was 61.5%. ICH patients without GFAP elevation had significantly smaller hemorrhage volumes (median 4.5 vs. 37.6 ml, p = 0.004) and were less likely to deteriorate (19 vs. 56%, p = 0.087). Conclusions: GFAP levels >0.29 ng/ml were seen only in ICH, thus confirming the diagnosis of ICH during prehospital care. However, sensitivity is low particularly in smaller hemorrhages.

Influence of Distance to Scene on Time to Thrombolysis in a Specialized Stroke Ambulance

Background and Purpose— Specialized computed tomography–equipped stroke ambulances shorten time to intravenous thrombolysis in acute ischemic stroke by starting treatment before hospital arrival. Because of longer travel-time-to-scene, time benefits of this concept are expected to diminish with longer distances from base station to scene. Methods— We used data from the Prehospital Acute Neurological Treatment and Optimization of Medical Cares in Stroke (PHANTOM-S) trial comparing time intervals between patients for whom a specialized stroke ambulance (stroke emergency mobile) was deployed and patients with conventional emergency medical service. Expected times from base station to scene had been calculated beforehand using computer algorithms informed by emergency medical service routine data. Four different deployment zones with–75% probability–expected arrival within 4, 8, 12, and 16 minutes and total population coverage of ≈1.3 million inhabitants were categorized for stroke emergency mobile deployment. We analyzed times from alarm-to-arrival at scene, to start of intravenous thrombolysis and from onset-to-intravenous thrombolysis. Results— Corresponding to the size of the respective catchment zone, the number of patients cared increased with distance (zone 1: n=30, zone 2: n=127, zone 3: n=156, and zone 4: n=217). Although time to stroke emergency mobile arrival increased with distance (mean: 8.0, 12.5, 15.4, and 18.4 minutes in zones 1–4), time from alarm-to-intravenous thrombolysis (mean: 41.8 versus 76.5; 50.2 versus 79.1; 54.5 versus 76.6; and 59.3 versus 78.0 minutes, respectively; all P<0.01) remained shorter in the stroke emergency mobile group across all zones. Conclusions— In a metropolitan area such as Berlin, time benefits justify a specialized stroke ambulance service up to a mean travel time of 18 minutes from base station. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01382862.