Factors associated with ventilator-associated events: an international multicenter prospective cohort study

  • Jordi Rello
  • Sergio Ramírez-Estrada
  • Anabel RomeroEmail author
  • Kostoula Arvaniti
  • Despoina Koulenti
  • Saad Nseir
  • Nefise Oztoprak
  • Lila Bouadma
  • Loreto Vidaur
  • Leonel Lagunes
  • Yolanda Peña-López
  • for the EUVAE Study Group
Original Article


A secondary analysis of a prospective multicenter cohort was performed in six intensive care units (ICU) in four European countries (France, Greece, Spain and Turkey). The main objective was to identify factors associated with ventilator-associated events (VAEs) in adults who underwent mechanical ventilation (MV) ≥ 48 h. Secondary objectives were to identify: variables influencing VAE in the subpopulation with endotracheal intubation and in those subjects who were ventilated > 7 days. Subjects who had undergone MV ≥ 48 h were included. In subjects with multiple episodes of MV, only the first one was eligible. The adult definitions for VAEs were adjusted to the 2015 update of the CDC’s 2013 National Healthcare Safety Network Association. Factors associated with VAE were estimated through multivariate Cox proportional hazards analysis. Among 163 adults (42 tracheostomies), 76 VAEs (34.9 VAEs/1,000 ventilator-days) were documented: 9 were Ventilator-Associated Conditions (VAC) and 67 Infection-related Ventilator-Associated Complications (IVAC)-plus (9 only IVAC and 58 Possible Ventilator-Associated Pneumonia). VAEs developed after a median of 6 days (interquartile range: 4–9). VAEs were independently associated with long-acting sedative/analgesic drugs (Hazard Ratio [HR]: 4.30), selective digestive decontamination (SDD) (HR: 0.38), and surgical/trauma admission (HR: 2.30). Among 116 subjects with endotracheal tube, SDD (HR: 0.21) and surgical/trauma admission (HR: 3.11) remained associated with VAE. Among 102 subjects ventilated >7 days, only long-acting sedative/analgesic agents (HR: 8.69) remained independently associated with VAE. In summary, SDD implementation and long-acting analgesic/sedative agents restriction prescription may prevent early and late VAEs, respectively. Bundles developed to prevent VAEs should include these two interventions.


Ventilator-associated pneumonia Selective digestive decontamination Midazolam Prevention bundles Mechanical ventilation Safety 



We thank Michael Maudsley for providing assistance with English language corrections to this manuscript. We also thank Santiago Pérez-Hoyos from the Statistics and Bio informatics Unit (UEB) at Vall d’Hebron Research Institute (VHIR) for giving statistical advice. This research was carried out as part of a PhD program in Health Science at the Universitat Autónoma de Barcelona, Spain, and was supported by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Critically Ill Patients (ESGCIP), Basel, Switzerland, and by Centro de Investigación Biomédica en Red—CIBERES CB06/06/036, Madrid, Spain.

We thank all EUVAE collaborators for collecting the data or scientific advice: Benito Almirante (Hospital Universitari Vall d’Hebron, Barcelona, Spain), Aliye Bastug (Ankara Numune Training and Research Hospital, Turkey), Mateo Bassetti (Santa Maria Misericordia Hospital, University of Udine, Udine, Italy), Ilkay Bozkurt (Ondokuz Mayis University, Samsun, Turkey), George Dimopoulos (Attikon University Hospital, Athens, Greece), Asuman Inan (Haydarpasa Numune Hospital, Istanbul, Turkey), Marina Oikonomou (Papageorgiou General Hospital, Thessaloniki, Greece), Garyphallia Poulakou (Attikon University Hospital, Athens, Greece), David Thompson (RBWH), Estefania Torrivilla (RBWH), Izarne Totorika (Hospital Universitario de Donostia, Donostia, Spain), and Vipin Varghese (RBWH).


Supported in part by grants from the European Society of Clinical Microbiology and Infectious Diseases—ESCMID, Study Group for Infections in Critically Ill Patients—ESGCIP, Basel, Switzerland, and by Centro de Investigación Biomédica en Red—CIBERES 06/06/036, Instituto Salud Carlos III, Madrid, Spain, and Fundació Catalana de Pneumologia—FUCAP, Barcelona, Spain.

Compliance with ethical standards

Conflict of interest

Dr. Rello has served on the speakers’ bureau and as a consultant for Cubist, Bayer, ROCHE, Medimmune, Pfizer, Anchoagen, and Aridis. The other authors report no conflicts of interest relevant to this article.

Ethical approval/informed consent

The study protocol was approved by the institutional review board on human research at each participating center and at Vall d’Hebron Barcelona Hospital Campus, the coordinating center [PR(AG)25/2014]. Patients (or the relatives of unconscious patients) were asked to provide written consent prior to participation in the study.

Supplementary material

10096_2019_3596_MOESM1_ESM.docx (36 kb)
ESM 1 (DOCX 36 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jordi Rello
    • 1
    • 2
    • 3
  • Sergio Ramírez-Estrada
    • 4
    • 5
  • Anabel Romero
    • 1
    • 2
    Email author
  • Kostoula Arvaniti
    • 3
    • 6
  • Despoina Koulenti
    • 3
    • 7
    • 8
    • 9
  • Saad Nseir
    • 10
  • Nefise Oztoprak
    • 11
  • Lila Bouadma
    • 12
  • Loreto Vidaur
    • 13
  • Leonel Lagunes
    • 3
    • 14
  • Yolanda Peña-López
    • 2
    • 15
  • for the EUVAE Study Group
  1. 1.Centro de Investigación Biomédica en Red—Enfermedades Respiratorias (CIBERES)Vall d’Hebron Research InstituteBarcelonaSpain
  2. 2.Vall d’Hebron Research Institute (VHIR)BarcelonaSpain
  3. 3.European Society of Clinical Microbiology and Infectious Diseases—Study Group for Infections in Critically Ill Patients (ESGCIP-ESCMID)BaselSwitzerland
  4. 4.Intensive Care DepartmentClinica CorachanBarcelonaSpain
  5. 5.Medicine DepartmentUniversitat Autònoma de BarcelonaBarcelonaSpain
  6. 6.Intensive Care UnitPapageorgiou HospitalThessalonikiGreece
  7. 7.Critical Care DepartmentAttikon University HospitalAthensGreece
  8. 8.UQ Centre for Clinical Research, Faculty of MedicineThe University of QueenslandBrisbaneAustralia
  9. 9.Royal Brisbane Clinical Unit, Faculty of MedicineThe University of QueenslandBrisbaneAustralia
  10. 10.Critical Care CenterHospital Universitaire LilleLilleFrance
  11. 11.Department of Infectious Diseases and Clinical Microbiology ClinicAntalya Education and Research HospitalAntalyaTurkey
  12. 12.Medical and Infectious Diseases ICU, Bichat-Claude-Bernard HospitalAssistance Publique-Hôpitaux de ParisParisFrance
  13. 13.Intensive Care DepartmentDonostia Univertsitate Ospitalea/CIBERESDonostiaSpain
  14. 14.Intensive Care Department Hospital Especialidades MédicasSan Luís PotosíMexico
  15. 15.Paediatric Critical Care DepartmentHospital Universitari Vall d’HebronBarcelonaSpain

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