Intensive Care Medicine

, Volume 43, Issue 11, pp 1602–1612 | Cite as

Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial

  • Frank Bloos
  • Hendrik Rüddel
  • Daniel Thomas-Rüddel
  • Daniel Schwarzkopf
  • Christine Pausch
  • Stephan Harbarth
  • Torsten Schreiber
  • Matthias Gründling
  • John Marshall
  • Philipp Simon
  • Mitchell M. Levy
  • Manfred Weiss
  • Andreas Weyland
  • Herwig Gerlach
  • Tobias Schürholz
  • Christoph Engel
  • Claudia Matthäus-Krämer
  • Christian Scheer
  • Friedhelm Bach
  • Reimer Riessen
  • Bernhard Poidinger
  • Karin Dey
  • Norbert Weiler
  • Andreas Meier-Hellmann
  • Helene H. Häberle
  • Gabriele Wöbker
  • Udo X. Kaisers
  • Konrad Reinhart
  • for the MEDUSA study group
Original

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) 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.

Keywords

Critical illness Septic shock/drug therapy Antimicrobial agents Quality improvement 

Supplementary material

134_2017_4782_MOESM1_ESM.docx (739 kb)
Supplementary material 1 (DOCX 738 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2017

Authors and Affiliations

  • Frank Bloos
    • 1
    • 2
  • Hendrik Rüddel
    • 1
    • 2
  • Daniel Thomas-Rüddel
    • 1
    • 2
  • Daniel Schwarzkopf
    • 1
  • Christine Pausch
    • 3
  • Stephan Harbarth
    • 4
  • Torsten Schreiber
    • 5
  • Matthias Gründling
    • 6
  • John Marshall
    • 7
  • Philipp Simon
    • 8
  • Mitchell M. Levy
    • 9
  • Manfred Weiss
    • 10
  • Andreas Weyland
    • 11
  • Herwig Gerlach
    • 12
  • Tobias Schürholz
    • 13
    • 14
  • Christoph Engel
    • 3
  • Claudia Matthäus-Krämer
    • 1
  • Christian Scheer
    • 6
  • Friedhelm Bach
    • 15
  • Reimer Riessen
    • 16
  • Bernhard Poidinger
    • 1
    • 2
  • Karin Dey
    • 17
  • Norbert Weiler
    • 18
  • Andreas Meier-Hellmann
    • 19
  • Helene H. Häberle
    • 20
  • Gabriele Wöbker
    • 21
  • Udo X. Kaisers
    • 8
    • 22
  • Konrad Reinhart
    • 1
    • 2
  • for the MEDUSA study group
  1. 1.Center for Sepsis Control and Care (CSCC)Jena University HospitalJenaGermany
  2. 2.Department of Anesthesiology and Intensive Care MedicineJena University HospitalJenaGermany
  3. 3.Institute for Medical Informatics, Statistics and EpidemiologyUniversity of LeipzigLeipzigGermany
  4. 4.Service Prévention et Contrôle de l’InfectionHôpitaux Universitaires de GenèveGenevaSwitzerland
  5. 5.Department of Anaesthesia and Intensive Care MedicineZentralklinik Bad Berka GmbHBad BerkaGermany
  6. 6.Department of Anesthesiology and Intensive Care MedicineUniversity Hospital GreifswaldGreifswaldGermany
  7. 7.Department of Surgery and the Li Ka Shing Knowledge Institute, St Michael’s HospitalUniversity of TorontoOntarioCanada
  8. 8.Department of Anesthesiology and Intensive Care MedicineUniversity Hospital LeipzigLeipzigGermany
  9. 9.Division of Pulmonary and Critical Care MedicineWarren Alpert Medical School of Brown UniversityProvidenceUSA
  10. 10.Department of AnesthesiologyUniversity Hospital UlmUlmGermany
  11. 11.Department of Anesthesiology and Intensive Care MedicineUniversity Hospital OldenburgOldenburgGermany
  12. 12.Department of Anesthesiology, Surgical Intensive Care Medicine and Pain TherapyVivantes Hospital NeuköllnBerlinGermany
  13. 13.Department of Intensive Care MedicineUniversity Hospital RWTH AachenAachenGermany
  14. 14.Department of Anesthesiology and Intensive Care MedicineUniversity Hospital RostockRostockGermany
  15. 15.Department of Anesthesiology, Intensive Care, Transfusion and Emergency Medicine and Pain TherapyBethel Hospital BielefeldBielefeldGermany
  16. 16.Department of Internal MedicineUniversity Hospital TübingenTübingenGermany
  17. 17.Department of Anesthesiology and Intensive Care MedicineHospital of the Bundeswehr BerlinBerlinGermany
  18. 18.Department of Anesthesiology and Intensive Care MedicineUniversity Medical Center KielKielGermany
  19. 19.Department of Anesthesiology, Intensive Care Medicine and Pain TherapyHelios Hospital ErfurtErfurtGermany
  20. 20.Department of Anesthesiology and Intensive Care MedicineUniversity Hospital TübingenTübingenGermany
  21. 21.Department of Intensive Care MedicineHelios Hospital WuppertalWuppertalGermany
  22. 22.University Hospital UlmUlmGermany

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