Lorenz Breuer

Avoiding in hospital delays and eliminating the three-hour effect in thrombolysis for stroke

Background Intravenous thrombolysis for acute stroke is more efficient the earlier the treatment is initiated. In-hospital delays account for a significant proportion of avoidable time loss before treatment is initiated. Paradoxically, studies have reported longer door-to-needle times the earlier the patients arrive (‘three-hour effect’). Hypothesis We hypothesized that a standardized thrombolysis procedure carried out in a specialized neurological emergency room can minimize in-hospital delays and erase the ‘three-hour effect’. Methods Onset-to-door and door-to-needle times of 246 consecutive thrombolysis patients were analyzed. A standardized protocol designed to minimize in-hospital delays was tested using a resident-based stroke team within a neurological emergency room. Correlation of onset-to-door and door-to-needle times was measured as well as differences in treatment times for daytime versus night hours and weekend vs. weekday. Outcome, rate of symptomatic intracranial hemorrhage and mortality were compared with the results of SITS-MOST. Results Median door-to-needle time was 25 min compared with a mean of 68 min in SITS-MOST. door-to-needle time did not correlate with onset-to-door time (Pearsons r=−0·097; P=0·13) and patients arriving within 90 min from symptom onset showed comparable door-to-needle times with patients arriving within 90–180 min. Neither treatment on weekends nor during night hours led to significant in-hospital treatment delays. Outcome and safety parameters were comparable with those observed in SITS-MOST. Conclusions By applying a standardized and diligently monitored thrombolysis protocol, carried out by a specialized stroke team within a neurological emergency room, in-hospital delays can be minimized. This allows improvement of door-to-needle times irrespective of the time to arrival and treatment during off-hours.

Serious Cardiac Arrhythmias After Stroke Incidence, Time Course, and Predictors—A Systematic, Prospective Analysis

Background and Purpose— Patients with acute cerebrovascular events are susceptible to serious cardiac arrhythmias, but data on the time course and the determinants of their onset are scarce. Methods— The prospective Stroke-Arrhythmia-Monitoring-Database (SAMBA) assessed cardiac arrhythmias with need for urgent evaluation and treatment in 501 acute neurovascular patients during the first 72 hours after admission to a monitored stroke unit. Arrhythmias were systematically detected by structured processing of telemetric data. Time of arrhythmia onset and predisposing factors were investigated. Results— Significant cardiac arrhythmias occurred in 25.1% of all patients. Incidence was highest during the first 24 hours after admission. Serious arrhythmic tachycardia (ventricular or supraventricular >130 beats/min) was more frequent than bradycardic arrhythmia (sinus-node dysfunction, bradyarrhythmia, or atrioventricular block °II and °III). Arrhythmias were independently associated with higher age and severer neurological deficits as measured by the National Institutes of Health Stroke Scale on admission. Conclusions— The risk for significant cardiac arrhythmia after an acute cerebrovascular event is highest during the first 24 hours of care and declines with time during the first 3 days. Along with established vascular risk factors, the National Institutes of Health Stroke Scale may be considered for a stratified allocation of monitoring capabilities. Clinical Trial Registration— URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

Feasibility and safety of magnetic resonance imaging-based thrombolysis in patients with stroke on awakening: initial single-centre experience

Background Up to 25% of all acute ischaemic strokes occur during sleep. Because of the unclear time window, patients with stroke on awakening are usually not considered for acute therapy and excluded from most acute treatment trials. Aim To evaluate the feasibility of magnetic resonance imaging-based intravenous thrombolysis in patients with stroke on awakening in a routine clinical setting. Methods Forty-five patients with stroke on awakening clinically qualifying for intravenous thrombolysis and presenting within 6 h after symptom recognition were admitted to our institution between October 2006 and May 2008. Following an institutional protocol, patients received magnetic resonance imaging as a first-line imaging modality and were offered mismatch-based thrombolysis whenever possible. Baseline demographic data, clinical, laboratory and imaging findings were analysed. Outcome was assessed using the modified Rankin Scale score at 3 months. Results Magnetic resonance imaging screening was feasible in 43/45 patients (96%). After screening, 10 patients (22%) were treated with intravenous thrombolysis. There were no differences between treated and untreated patients regarding cardiovascular risk factors, stroke aetiology, previous prophylactic treatment and symptom recognition to door time or door to imaging time. Outcome was comparable in both groups despite a trend towards more severe strokes in the intravenous thrombolysis group. Only one asymptomatic and no symptomatic haemorrhage were observed. Conclusion Our data demonstrate that magnetic resonance imaging-based thrombolysis is feasible and possibly safe in patients with stroke on awakening (SOA). Randomised clinical trials for patients with stroke on awakening are needed to further test the safety and efficacy of intravenous thrombolysis in this patient group. The results of our study may help to initiate and design such studies.

Off-Label Thrombolysis for Acute Ischemic Stroke: Rate, Clinical Outcome and Safety Are Influenced by the Definition of ‘Minor Stroke’

Background: Several contraindications for intravenous thrombolysis are not based on controlled trials. Specialized stroke centers often apply less restrictive criteria. The aim of our study was to analyze how many patients at our institution receive off-label thrombolysis. In addition, clinical outcome and safety data were compared to those from patients treated on-label, and the influence of different definitions of ‘minor stroke’ were examined. Methods: Consecutive thrombolysis patients treated between January 2006 and January 2010 were included. Patients treated off-label were compared to patients given on-label therapy according to the European license. Since no specified definition for ‘minor neurological deficit’ exists in the license, two distinct definitions were considered off-label, i.e. National Institutes of Health Stroke Scale score (NIHSSS) <1 (definition 1) and NIHSSS ≤4 (definition 2). Results: Of a total of 422 patients, 232 (55%) were treated off-label. The most prevalent off-label criteria (OLCs) were the following: age >80 years (n = 113), minor stroke (definition 1, n = 3; definition 2, n = 84), elevated blood pressure necessitating aggressive treatment (n = 75), time window >3 h (n = 71) and major surgery or trauma within the preceding 3 months (n = 20). In group comparisons, off-label patients had an overall worse outcome using definition 1 for minor stroke, while there was no difference when definition 2 was applied. In multivariate analysis, off-label therapy (definition 1) in general and age >80 years were independent predictors of poor outcome. None of the contraindications were associated with an increased bleeding risk. Conclusions: Off-label therapy is frequently applied at our center and is not associated with higher complication rates. Overall outcome of off-label treatment largely depends on the definition used for minor stroke. Besides age >80 years, a known poor prognostic factor, no other specific OLC was associated with poor outcome. Our data suggest that the criteria in the European license may be too restrictive.

A Structured Reading Algorithm Improves Telemetric Detection of Atrial Fibrillation After Acute Ischemic Stroke

Background and Purpose— Anticoagulation is a highly effective secondary prevention in patients with cardioembolic stroke and atrial fibrillation/flutter (AF). However, the condition remains underdiagnosed, because paroxysmal AF may be missed by diagnostic tests in the acute phase. In this study, the sensitivity of AF detection was assessed for serial electrocardiographic recordings and continuous stroke unit telemetric monitoring with or without a structured algorithm to analyze telemetric data (SEA-AF). Methods— Three hundred forty-six consecutive patients with acute ischemic stroke were prospectively included and subjected to standard telemetric monitoring. In addition, telemetric data were separately analyzed following SEA-AF, consisting of a structured evaluation of episodes with high risk for AF and a chronological beat-to-beat screening of the full registration. Serial electrocardiograms were conducted in 24-hour intervals. Results— Median effective telemetry monitoring time was 75.5 hours (interquartile range 64–86 hours). Overall, AF was diagnosed in 119 of 346 patients (34.4%). The structured reading algorithm was the most sensitive method to detected AF. Conventional telemetry and serial electrocardiographic assessments were less effective. However, only 35% of patients with previously documented paroxysmal AF and negative baseline electrocardiogram demonstrated AF episodes during monitoring. Conclusions— Continuous stroke unit telemetry using SEA-AF shows a significantly higher detection rate for AF compared with daily electrocardiographic assessments and standard telemetry without structured reading. The low overall probability to detect paroxysmal AF with either method during the first days after stroke demonstrates the urgent need for complementary diagnostic strategies such as long-term monitoring and frequent follow-up assessments. Clinical Trial Registration— URL: www.clinicaltrials.gov. Unique identifier: NCT01177748.

Weight Approximation in Stroke Before Thrombolysis The WAIST-Study: A Prospective Observational “Dose-Finding” Study

Background and Purpose— Because of the narrow therapeutic range for thrombolysis in stroke, accurate weight-based dosing is essential for efficacy and safety. Stroke patients are frequently incapable to communicate their correct body weight (BW). Thus, dosing is often based on BW estimation, which may lead to dosing errors. The aim of our study was to evaluate availability of BW information, accuracy of estimations, and final dosing of Alteplase (tissue plasminogen activator [tPA]) in a routine clinical setting. Methods— A total of 109 consecutive intravenous thrombolysis patients were prospectively included in the study. Recruitment concluded with 100 complete data sets. Before therapy, BW was estimated independently by 2 physicians, 2 emergency nurses, and a neuroradiological technical assistant. Patients were weighed, and anthropometric measurements for BW approximation were taken. Dosing errors were assessed. Clinical outcome was evaluated at 90 days. Results— Of 109 patients, 55 (50.5%) were unable to provide information on their BW. Of those, 11 (20%) were accompanied by relatives able to give BW information. For all patients, estimation errors rates ranged from 20.8% (patients own estimation) up to 38.2% (treating physician) and 42.2% (emergency nurse). Finally, 29 patients received an Alteplase dosage diverging >10% from the optimal dose. Twelve were under- and 17 overdosed. Underdosage was an independent predictor for worse outcome in multivariate analysis. Conclusions— Our study shows that reliable BW data are missing for a majority of intravenous thrombolysis patients. Measuring BW before administering Alteplase remains challenging. Given dosing errors in one-third of patients and the observed impact on outcome, standardized weighing before thrombolysis should be considered. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006434.

Ischemic Stroke in an Obese Patient Receiving Dabigatran

An obese man (BMI, 44.7) with atrial fibrillation who was receiving dabigatran for thromboprophylaxis presented with an ischemic stroke. Dabigatran levels during observed administration were less than the 25th percentile of the therapeutic trough level.

Characteristics and outcome of patients with early complete neurological recovery after thrombolysis for acute ischemic stroke.

Background: Recombinant tissue plasminogen activator (rt-PA) is the only approved specific therapy for acute ischemic stroke. This study analyzes demographic and clinical characteristics of patients with early complete neurological recovery after thrombolysis. Methods: Data of 320 consecutive patients treated with rt-PA within 3 h of stroke onset at our facility between April 2006 and March 2009 were extracted from our prospective institutional stroke and thrombolysis database. Baseline demographic parameters, risk factors, clinical characteristics as well as neuroradiologic findings of patients with complete recovery 24 h after treatment and at hospital discharge were analyzed. Outcome was evaluated using the modified Rankin Scale at 90 days. Results: Thirty patients (9.4%) were asymptomatic 24 h after thrombolysis and 70 (22%) at hospital discharge. Patients with complete recovery were younger, more often male, had milder stroke symptoms, less often cardioembolic strokes, fewer bleeding complications and more often normal follow-up imaging. In addition, in-hospital time was shorter and these patients retained a better functional outcome at 90 days. Only 1 patient who had completely recovered at hospital discharge died during the follow-up time. In multivariate regression analysis, only the National Institute of Health Stroke Score (NIHSS) on admission was predictive for complete recovery at both examined time points. Conclusion: Rapid complete recovery can be achieved in up to a fifth of acute stroke patients treated with thrombolysis. These patients are younger and have milder strokes, less often with cardioembolic origin. Better outcome and lower mortality are sustained at 3 months.

Validation of the DRAGON Score in 12 Stroke Centers in Anterior and Posterior Circulation

Background and Purpose— The DRAGON score predicts functional outcome in the hyperacute phase of intravenous thrombolysis treatment of ischemic stroke patients. We aimed to validate the score in a large multicenter cohort in anterior and posterior circulation. Methods— Prospectively collected data of consecutive ischemic stroke patients who received intravenous thrombolysis in 12 stroke centers were merged (n=5471). We excluded patients lacking data necessary to calculate the score and patients with missing 3-month modified Rankin scale scores. The final cohort comprised 4519 eligible patients. We assessed the performance of the DRAGON score with area under the receiver operating characteristic curve in the whole cohort for both good (modified Rankin scale score, 0–2) and miserable (modified Rankin scale score, 5–6) outcomes. Results— Area under the receiver operating characteristic curve was 0.84 (0.82–0.85) for miserable outcome and 0.82 (0.80–0.83) for good outcome. Proportions of patients with good outcome were 96%, 93%, 78%, and 0% for 0 to 1, 2, 3, and 8 to 10 score points, respectively. Proportions of patients with miserable outcome were 0%, 2%, 4%, 89%, and 97% for 0 to 1, 2, 3, 8, and 9 to 10 points, respectively. When tested separately for anterior and posterior circulation, there was no difference in performance (P=0.55); areas under the receiver operating characteristic curve were 0.84 (0.83–0.86) and 0.82 (0.78–0.87), respectively. No sex-related difference in performance was observed (P=0.25). Conclusions— The DRAGON score showed very good performance in the large merged cohort in both anterior and posterior circulation strokes. The DRAGON score provides rapid estimation of patient prognosis and supports clinical decision-making in the hyperacute phase of stroke care (eg, when invasive add-on strategies are considered).

Relationship Between Onset-to-Door Time and Door-to-Thrombolysis Time: A Pooled Analysis of 10 Dedicated Stroke Centers

Background and Purpose— Inverse relationship between onset-to-door time (ODT) and door-to-needle time (DNT) in stroke thrombolysis was reported from various registries. We analyzed this relationship and other determinants of DNT in dedicated stroke centers. Methods— Prospectively collected data of consecutive ischemic stroke patients from 10 centers who received IV thrombolysis within 4.5 hours from symptom onset were merged (n=7106). DNT was analyzed as a function of demographic and prehospital variables using regression analyses, and change over time was considered. Results— In 6348 eligible patients with known treatment delays, median DNT was 42 minutes and kept decreasing steeply every year (P<0.001). Median DNT of 55 minutes was observed in patients with ODT ⩽30 minutes, whereas it declined for patients presenting within the last 30 minutes of the 3-hour time window (median, 33 minutes) and of the 4.5-hour time window (20 minutes). For ODT within the first 30 minutes of the extended time window (181–210 minutes), DNT increased to 42 minutes. DNT was stable for ODT for 30 to 150 minutes (40–45 minutes). We found a weak inverse overall correlation between ODT and DNT (R2=−0.12; P<0.001), but it was strong in patients treated between 3 and 4.5 hours (R2=−0.75; P<0.001). ODT was independently inversely associated with DNT (P<0.001) in regression analysis. Octogenarians and women tended to have longer DNT. Conclusions— DNT was decreasing steeply over the last years in dedicated stroke centers; however, significant oscillations of in-hospital treatment delays occurred at both ends of the time window. This suggests that further improvements can be achieved, particularly in the elderly.