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Cerebrovascular Disease

Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin

Educational Objective
To learn about the performance of mobile stroke units.

1 Credit CME

JAMA

Published Online: February 2, 2021

Original Investigation

Article Information and Disclosures

Martin Ebinger, MD^1,2;

Bob Siegerink, PhD¹;

Alexander Kunz, MD^1,2;

Matthias Wendt, MD³;

Joachim E. Weber, MD^4,8;

Eugen Schwabauer, MD⁵;

Frederik Geisler, MD⁴;

Erik Freitag, MD⁴;

Julia Lange, MD⁴;

Janina Behrens, MD⁴;

Hebun Erdur, MD⁴;

Ramanan Ganeshan, MD⁴;

Thomas Liman, MD⁴;

Jan F. Scheitz, MD^1,4;

Ludwig Schlemm, MD^1,4;

Peter Harmel, MD⁴;

Katja Zieschang, MD³;

Irina Lorenz-Meyer, MSc⁴;

Ira Napierkowski, Dr rer nat⁴;

Carolin Waldschmidt, MD^4,6;

Christian H. Nolte, MD^1,4,7,8;

Ulrike Grittner, DrPhil^7,9;

Edzard Wiener, MD¹⁰;

Georg Bohner, MD¹⁰;

Darius G. Nabavi, MD⁵;

Ingo Schmehl, MD³;

Axel Ekkernkamp, MD³;

Gerhard J. Jungehulsing, MD¹¹;

Bruno-Marcel Mackert, MD¹²;

Andreas Hartmann, MD¹³;

Jessica L. Rohmann, MScPH^1,14;

Matthias Endres, MD^{1,4,7,8,15,16};

Heinrich J. Audebert, MD^1,4;

for the Berlin_PRehospital Or Usual Delivery in stroke care (B_PROUD) study group

Author Affiliations

¹Center for Stroke Research Berlin, Charité–Universitätsmedizin Berlin, Germany
²Klinik für Neurologie, Medical Park Berlin Humboldtmühle, Berlin, Germany
³Klinik für Neurologie mit Stroke Unit und Frührehabilitation, Unfallkrankenhaus Berlin, Germany
⁴Klinik und Hochschulambulanz für Neurologie, Charité–Universitätsmedizin Berlin, Germany
⁵Klinik für Neurologie mit Stroke Unit, Vivantes Klinikum Neukölln, Berlin, Germany
⁶Klinik für Neurologie–Stroke Unit–Zentrum für Epilepsie; Vivantes Humboldt-Klinikum, Berlin, Germany
⁷Berlin Institute of Health (BIH), Berlin, Germany
⁸German Centre for Cardiovascular Research (DZHK), partner site Berlin, Germany
⁹Institute of Biometry and Clinical Epidemiology, Charité - Universitätsmedizin Berlin, Germany
¹⁰Institut für Neuroradiologie, Charité–Universitätsmedizin Berlin, Germany
¹¹Klinik für Neurologie, Jüdisches Krankenhaus Berlin, Germany
¹²Klinik für Neurologie mit Stroke Unit, Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany
¹³Klinik für Neurologie, Klinikum Frankfurt (Oder), Germany
¹⁴Institute of Public Health, Charité–Universitätsmedizin Berlin, Germany
¹⁵NeuroCure Cluster of Excellence, Berlin, Germany
¹⁶German Center for Neurodegenerative Diseases (DZNE), partner site Berlin, Germany

Berlin_PRehospital Or Usual Delivery in stroke care (B_PROUD) study groupfor the

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Key Points

Question Is the dispatch of mobile stroke units in the out-of-hospital setting before arriving at the hospital associated with better functional outcomes among patients with acute ischemic stroke eligible for thrombolysis or thrombectomy?

Findings In this prospective nonrandomized controlled intervention study involving 1543 patients in Berlin, Germany, the dispatch of mobile stroke units in addition to conventional ambulances vs conventional ambulances alone was significantly associated with lower levels of global disability at 3 months (common odds ratio for higher modified Rankin Scale scores [ie, worse outcome], 0.71).

Meaning Among patients with acute ischemic stroke in Berlin, Germany, dispatch of a mobile stroke unit was associated with lower global disability at 3 months; further research in diverse settings is needed.

Abstract

Importance Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment.

Objective To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke.

Design, Setting, and Participants This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only).

Exposure Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794).

Main Outcomes and Measures The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability.

Results Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04).

Conclusions and Relevance In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.

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Article Information

Corresponding Author: Heinrich J. Audebert, MD, Klinik und Hochschulambulanz für Neurologie, Charité–Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany (heinrich.audebert@charite.de).

Correction: This article was corrected on April 6, 2021, to add the group name and make other minor edits.

Accepted for Publication: December 18, 2020.

Author Contributions: Dr Audebert had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Ebinger, Siegerink, Behrens, Nolte, Wiener, Nabavi, Endres, Audebert.

Acquisition, analysis, or interpretation of data: Ebinger, Siegerink, Kunz, Wendt, Weber, Schwabauer, Geisler, Freitag, Lange, Erdur, Ganeshan, Liman, Scheitz, Schlemm, Harmel, Zieschang, Lorenz-Meyer, Napierkowski, Waldschmidt, Nolte, Grittner, Wiener, Bohner, Schmehl, Ekkernkamp, Jungehulsing, Mackert, Hartmann, Rohmann, Audebert.

Drafting of the manuscript: Ebinger, Grittner, Wiener, Rohmann.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Siegerink, Napierkowski, Grittner, Rohmann, Audebert.

Obtained funding: Ebinger, Harmel, Endres, Audebert.

Administrative, technical, or material support: Kunz, Wendt, Weber, Schwabauer, Geisler, Freitag, Behrens, Ganeshan, Liman, Harmel, Lorenz-Meyer, Napierkowski, Waldschmidt, Nolte, Nabavi, Ekkernkamp, Jungehulsing, Mackert, Audebert.

Supervision: Ebinger, Siegerink, Wendt, Freitag, Nolte, Wiener, Nabavi, Schmehl, Ekkernkamp, Jungehulsing, Endres, Audebert.

Other - epidemiological expertise, tables and figures: Rohmann.

Other: Hartmann.

Conflict of Interest Disclosures: Drs Ebinger, Siegerink, Kunz, Weber, Geisler, Freitag, Erdur, Ganeshan, Schlemm, Harmel, Lorenz-Meyer, Napierkowski, Waldschmidt, Endres, and Audebert reported receiving institutional grants from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) and the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) during the conduct of the study. Dr Geisler reported receiving other support from Johnson and Johnson and AbbVie. Dr Scheitz reported receiving personal fees from Bristol Myers Squibb and Stryker GmbH & Co KG. Dr Schlemm reported receiving personal fees from Daiichi Sankyo. Dr Nolte reported receiving personal fees from Boehringer Ingelheim, Bristol Myers Squibb, Pfizer Pharma, and Abbott and research grants from the German Ministry of Research and Education, the German Center for Neurodegenerative Diseases, and the German Center for Cardiovascular Research. Dr Grittner reported receiving personal fees from Centogene AG, Rostock, Germany. Ms Rohmann reported receiving a grant from Novartis Pharma for conducting a self-initiated research project on migraine remission in aging. Dr Endres reported receiving grantEXC-2049–390688087 from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy (NeuroCure) Charité–Universitätsmedizin Berlin and from Bundesministerium für Bildung und Forschung (BMBF; German Ministry for Education and Research) for the Center for Stroke Research Berlin and grants from Bayer and other support from Bayer Boehringer Ingelheim, BMS, Pfizer, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, Novartis. Dr Audebert reported receiving personal fees from Bayer Vital, Boehringer Ingelheim, Bristol Myers Squibb, Novo Nordisk, Pfizer, and Sanofi. No other disclosures were reported.

Funding/Support: The B_PROUD study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), the B-SPATIAL registry, by the Federal Ministry of Education and Research via the Center for Stroke Research Berlin. Additional analyses requested during the review process and performed by the Institut für Biometrie und klinische Epidemiologie, Charité—Universitätsmedizin Berlin was funded by the Verein zur Förderung der Hirnforschung und Rehabilitation e.V.

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank the Berlin Fire Brigade, responsible for the Berlin Dispatch Center and EMS, for continuous collaboration and support. We thank Farid I. Kandil, Dr rer nat, Dipl Psych, Charité–Universitätsmedizin Berlin, for support with the forest plots; the Berlin Data Protection Office (Berliner Beauftragte für Datenschutz und Informationsfreiheit) for advice; Janet Fahron, data protection officer of the Charité–Universitätsmedizin Berlin, for her continuous support in advising and consulting; the Berlin Technology Foundation and Berlin Partner for funding of previous stages of the Berlin STEMO project, none of whom received compensation for their role in the study. Finally, we thank all collaborating hospitals and the study nurses for their support.

Additional Information: The investigators at the trial sites listed in the Supplement 3 were responsible for collecting the data.

External Statistical Reviewer: André Karch, MSc, Clinical Epidemiology, University of Muenster, Muenster, Germany.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.