Frank Bloos1,2, Hendrik Rüddel1,2, Daniel Thomas-Rüddel1,2, Daniel Schwarzkopf1, Christine Pausch3, Stephan Harbarth4, Torsten Schreiber5, Matthias Gründling6, John Marshall7, Philipp Simon8, Mitchell M Levy9, Manfred Weiss10, Andreas Weyland11, Herwig Gerlach12, Tobias Schürholz13,14, Christoph Engel3, Claudia Matthäus-Krämer1, Christian Scheer6, Friedhelm Bach15, Reimer Riessen16, Bernhard Poidinger1,2, Karin Dey17, Norbert Weiler18, Andreas Meier-Hellmann19, Helene H Häberle20, Gabriele Wöbker21, Udo X Kaisers8,22, Konrad Reinhart23,24. 1. Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany. 2. Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany. 3. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany. 4. Service Prévention et Contrôle de l'Infection, Hôpitaux Universitaires de Genève, Geneva, Switzerland. 5. Department of Anaesthesia and Intensive Care Medicine, Zentralklinik Bad Berka GmbH, Bad Berka, Germany. 6. Department of Anesthesiology and Intensive Care Medicine, University Hospital Greifswald, Greifswald, Germany. 7. Department of Surgery and the Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Ontario, Canada. 8. Department of Anesthesiology and Intensive Care Medicine, University Hospital Leipzig, Leipzig, Germany. 9. Division of Pulmonary and Critical Care Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA. 10. Department of Anesthesiology, University Hospital Ulm, Ulm, Germany. 11. Department of Anesthesiology and Intensive Care Medicine, University Hospital Oldenburg, Oldenburg, Germany. 12. Department of Anesthesiology, Surgical Intensive Care Medicine and Pain Therapy, Vivantes Hospital Neukölln, Berlin, Germany. 13. Department of Intensive Care Medicine, University Hospital RWTH Aachen, Aachen, Germany. 14. Department of Anesthesiology and Intensive Care Medicine, University Hospital Rostock, Rostock, Germany. 15. Department of Anesthesiology, Intensive Care, Transfusion and Emergency Medicine and Pain Therapy, Bethel Hospital Bielefeld, Bielefeld, Germany. 16. Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany. 17. Department of Anesthesiology and Intensive Care Medicine, Hospital of the Bundeswehr Berlin, Berlin, Germany. 18. Department of Anesthesiology and Intensive Care Medicine, University Medical Center Kiel, Kiel, Germany. 19. Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Helios Hospital Erfurt, Erfurt, Germany. 20. Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Tübingen, Germany. 21. Department of Intensive Care Medicine, Helios Hospital Wuppertal, Wuppertal, Germany. 22. University Hospital Ulm, Ulm, Germany. 23. Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany. konrad.reinhart@med.uni-jena.de. 24. Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany. konrad.reinhart@med.uni-jena.de.
Abstract
PURPOSE: Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. METHODS: The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) withconventional CME (n = 1587). The primary outcome was 28-day mortality. RESULTS: The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1-4.9 h) in the intervention group and 2.0 h (0.4-5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. CONCLUSIONS: Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.
RCT Entities:
PURPOSE: Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations. METHODS: The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality. RESULTS: The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1-4.9 h) in the intervention group and 2.0 h (0.4-5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment. CONCLUSIONS: Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.
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