Intensive Care Medicine

, Volume 43, Issue 7, pp 957–970 | Cite as

A multi-faceted strategy to reduce ventilation-associated mortality in brain-injured patients. The BI-VILI project: a nationwide quality improvement project

  • Karim AsehnouneEmail author
  • Ségolène Mrozek
  • Pierre François Perrigault
  • Philippe Seguin
  • Claire Dahyot-Fizelier
  • Sigismond Lasocki
  • Anne Pujol
  • Mathieu Martin
  • Russel Chabanne
  • Laurent Muller
  • Jean Luc Hanouz
  • Emmanuelle Hammad
  • Bertrand Rozec
  • Thomas Kerforne
  • Carole Ichai
  • Raphael Cinotti
  • Thomas Geeraerts
  • Djillali Elaroussi
  • Paolo Pelosi
  • Samir Jaber
  • Marie Dalichampt
  • Fanny Feuillet
  • Véronique Sebille
  • Antoine Roquilly
  • The BI-VILI study group
Seven-Day Profile Publication



We assessed outcomes in brain-injured patients after implementation of a multi-faceted approach to reduce respiratory complications in intensive care units.


Prospective nationwide before–after trial. Consecutive adults with acute brain injury requiring mechanical ventilation for ≥24 h in 20 French intensive care units (ICUs) were included. The management of invasive ventilation in brain-injured patients admitted between 1 July 2013 and 31 October 2013 (4 months) was monitored and analysed. After the baseline period (1 November 2013–31 December 2013), ventilator settings and decision to extubate were selected as targets to hasten weaning from invasive ventilation. During the intervention period, low tidal volume (≤7 ml/kg), moderate positive end-expiratory pressure (PEEP, 6–8 cm H2O) and an early extubation protocol were recommended. The primary endpoint was the number of days free of invasive ventilation at day 90. Comparisons were performed between the two periods and between the compliant and non-compliant groups.


A total of 744 patients from 20 ICUs were included (391 pre-intervention; 353 intervention). No difference in the number of invasive ventilation-free days at day 90 was observed between the two periods [71 (0–80) vs. 67 (0–80) days; P = 0.746]. Compliance with the complete set of recommendations increased from 8 (2%) to 52 (15%) patients after the intervention (P < 0.001). At day 90, the number of invasive ventilation-free days was higher in the 60 (8%) patients whose care complied with recommendations than in the 684 (92%) patients whose care deviated from recommendations [77 (66–82) and 71 (0–80) days, respectively; P = 0.03]. The mortality rate was 10% in the compliant group and 26% in the non-compliant group (P = 0.023). Both multivariate analysis [hazard ratio (HR) 1.78, 95% confidence interval (95% CI) 1.41–2.26; P < 0.001] and propensity score-adjusted analysis (HR 2.25, 95% CI 1.56–3.26, P < 0.001) revealed that compliance was an independent factor associated with the reduction in the duration of mechanical ventilation.


Adherence to recommendations for low tidal volume, moderate PEEP and early extubation seemed to increase the number of ventilator-free days in brain-injured patients, but inconsistent adoption limited their impact.

Trail registration number: NCT01885507.


Ventilator weaning Brain injuries Airway extubation Tidal volume PEEP 



The authors thank Delphine Flattres Duchaussoy, Sabrina Lebouter-Banon and the nurses of the participating ICUs for technical support.

BI-VILI study group

Dr. L. Thioliere L, Angers University Hospital; Dr. G. Zamparini G, Caen University Hospital; Dr. M. Leone, Marseille University Hospital; Drs. P.J. Mahe, D. Demeure dit latte and A. Delater, Nantes University Hospital, Hôtel Dieu; Drs. K. Lakhal K and L. Brisard, Nantes University Hospital, HGRL; Drs. R. Drilleau and O. Mimoz, Poitiers University Hospital; Drs. Y. Malledant, S. Isslame, Y. Launey and N. Nesseler, Rennes University Hospital; Dr. M. Ferrandière. Tours University Hospital.

Author contributions

RA was the principle investigator who oversaw the study conduct, helped develop all study materials including the trial protocol, assisted with participant recruitment and data collection at the Nantes site, participated in data analysis and interpretation of the results and drafted and revised the manuscript. AK provided oversight on trial design, helped develop study materials including the trial protocol, provided oversight on trial conduct, participated in data analysis and the interpretation of the results and revised the manuscript. FF, DM and SV were the trial statisticians and provided advice and input related to all statistical issues, completed final data analysis and interpretation of the results and revised the manuscript. MS, PFP, SP, DFC, LS, PA, MM, CR, ML, HJL, HE, RB, KT, IC, CR, GT and LM were the principal investigators at research sites and assisted with the development of the protocol and other study materials, referred or actively recruited participants at sites, assessed participant eligibility and delivered formal training. JS provided oversight on trial design, participated in data analysis and the interpretation of the results and revised the manuscript. FFV, LM, JPE and PP participated in the realisation of the meta-analysis and in the interpretation of the results and revised the manuscript.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.


Non-profit organization “Gueules Cassées”.

Data sharing

To access to the study date, please contact the corresponding author (AK) who has the full access to the raw data.

Supplementary material

134_2017_4764_MOESM1_ESM.pdf (417 kb)
Supplementary material 1 (PDF 416 kb)
134_2017_4764_MOESM2_ESM.docx (101 kb)
Supplementary material 2 (DOCX 101 kb)
134_2017_4764_MOESM3_ESM.docx (61 kb)
Supplementary material 3 (DOCX 60 kb)
134_2017_4764_MOESM4_ESM.docx (14 kb)
Supplementary material 4 (DOCX 15 kb)


  1. 1.
    Esteban A, Anzueto A, Frutos F et al (2002) Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA 287:345–355CrossRefPubMedGoogle Scholar
  2. 2.
    Middleton S, McElduff P, Ward J et al (2011) Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomised controlled trial. Lancet 378:1699–1706. doi: 10.1016/S0140-6736(11)61485-2 CrossRefPubMedGoogle Scholar
  3. 3.
    Kahn JM, Caldwell EC, Deem S et al (2006) Acute lung injury in patients with subarachnoid hemorrhage: incidence, risk factors, and outcome. Crit Care Med 34:196–202. doi: 10.1097/01.CCM.0000194540.44020.8E CrossRefPubMedGoogle Scholar
  4. 4.
    Mrozek S, Constantin J-M, Geeraerts T (2015) Brain-lung crosstalk: implications for neurocritical care patients. World J Crit Care Med 4:163–178. doi: 10.5492/wjccm.v4.i3.163 PubMedPubMedCentralGoogle Scholar
  5. 5.
    Roquilly A, Cinotti R, Jaber S et al (2013) Implementation of an evidence-based extubation readiness bundle in 499 brain-injured patients: a before-after evaluation of a quality improvement project. Am J Respir Crit Care Med 188:958–966. doi: 10.1164/rccm.201301-0116OC CrossRefPubMedGoogle Scholar
  6. 6.
    Serpa Neto A, Cardoso SO, Manetta JA et al (2012) Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA 308:1651–1659. doi: 10.1001/jama.2012.13730 CrossRefPubMedGoogle Scholar
  7. 7.
    Zygun DA, Kortbeek JB, Fick GH et al (2005) Non-neurologic organ dysfunction in severe traumatic brain injury. Crit Care Med 33:654–660. doi: 10.1097/01.CCM.0000155911.01844.54 CrossRefPubMedGoogle Scholar
  8. 8.
    Connolly ES, Rabinstein AA, Carhuapoma JR et al (2012) Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke 43:1711–1737. doi: 10.1161/STR.0b013e3182587839 CrossRefPubMedGoogle Scholar
  9. 9.
    Brain Trauma Foundation American Association of Neurological Surgeons, Congress of Neurological Surgeons (2007) Guidelines for the management of severe traumatic brain injury. J Neurotrauma 24[Suppl 1]:S1–S106. doi: 10.1089/neu.2007.9999 Google Scholar
  10. 10.
    Pelosi P, Ferguson ND, Frutos-Vivar F et al (2011) Management and outcome of mechanically ventilated neurologic patients. Crit Care Med 39:1482–1492. doi: 10.1097/CCM.0b013e31821209a8 CrossRefPubMedGoogle Scholar
  11. 11.
    Coplin WM, Pierson DJ, Cooley KD et al (2000) Implications of extubation delay in brain-injured patients meeting standard weaning criteria. Am J Respir Crit Care Med 161:1530–1536. doi: 10.1164/ajrccm.161.5.9905102 CrossRefPubMedGoogle Scholar
  12. 12.
    Navalesi P, Frigerio P, Moretti MP et al (2008) Rate of reintubation in mechanically ventilated neurosurgical and neurologic patients: evaluation of a systematic approach to weaning and extubation. Crit Care Med 36:2986–2992. doi: 10.1097/CCM.0b013e31818b35f2 CrossRefPubMedGoogle Scholar
  13. 13.
    Namen AM, Ely EW, Tatter SB et al (2001) Predictors of successful extubation in neurosurgical patients. Am J Respir Crit Care Med 163:658–664. doi: 10.1164/ajrccm.163.3.2003060 CrossRefPubMedGoogle Scholar
  14. 14.
    Salam A, Tilluckdharry L, Amoateng-Adjepong Y, Manthous C (2004) Neurologic status, cough, secretions and extubation outcomes. Intensive Care Med 30:1–6. doi: 10.1007/s00134-004-2231-7 CrossRefGoogle Scholar
  15. 15.
    Contentin L, Ehrmann S, Giraudeau B (2014) Heterogeneity in the definition of mechanical ventilation duration and ventilator-free days. Am J Respir Crit Care Med 189:998–1002. doi: 10.1164/rccm.201308-1499LE CrossRefPubMedGoogle Scholar
  16. 16.
    American Thoracic Society, Infectious Diseases Society of America (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 171:388–416. doi: 10.1164/rccm.200405-644ST CrossRefGoogle Scholar
  17. 17.
    Austin PC (2013) The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Statist Med 33:1242–1258. doi: 10.1002/sim.5984 CrossRefGoogle Scholar
  18. 18.
    Steyerberg EW, Mushkudiani N, Perel P et al (2008) Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics. PLoS Med 5:e165. doi: 10.1371/journal.pmed.0050165 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    The Acute Respiratory Distress Syndrome Network (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342:1301–1308. doi: 10.1056/NEJM200005043421801
  20. 20.
    Serpa Neto A, Hemmes SNT, Barbas CSV et al (2014) Incidence of mortality and morbidity related to postoperative lung injury in patients who have undergone abdominal or thoracic surgery: a systematic review and meta-analysis. Lancet Respir Med 2:1007–1015. doi: 10.1016/S2213-2600(14)70228-0 CrossRefPubMedGoogle Scholar
  21. 21.
    Amato MBP, Meade MO, Slutsky AS et al (2015) Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 372:747–755. doi: 10.1056/NEJMsa1410639 CrossRefPubMedGoogle Scholar
  22. 22.
    Mascia L, Zavala E, Bosma K et al (2007) High tidal volume is associated with the development of acute lung injury after severe brain injury: an international observational study. Crit Care Med 35:1815–1820. doi: 10.1097/01.CCM.0000275269.77467.DF CrossRefPubMedGoogle Scholar
  23. 23.
    Marhong JD, Ferguson ND, Singh JM (2014) Ventilation practices in subarachnoid hemorrhage: a cohort study exploring the use of lung protective ventilation. Neurocrit Care 21:178–185. doi: 10.1007/s12028-014-0014-8 CrossRefPubMedGoogle Scholar
  24. 24.
    Elmer J, Hou P, Wilcox SR et al (2013) Acute respiratory distress syndrome after spontaneous intracerebral hemorrhage. Crit Care Med 41:1992–2001. doi: 10.1097/CCM.0b013e31828a3f4d CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Chesnut RM, Marshall LF, Klauber MR et al (1993) The role of secondary brain injury in determining outcome from severe head injury. J Trauma 34:216–222CrossRefPubMedGoogle Scholar
  26. 26.
    Briel M, Meade M, Mercat A et al (2010) Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 303:865–873. doi: 10.1001/jama.2010.218 CrossRefPubMedGoogle Scholar
  27. 27.
    Manzano F, Fernández-Mondéjar E, Colmenero M et al (2008) Positive-end expiratory pressure reduces incidence of ventilator-associated pneumonia in nonhypoxemic patients. Crit Care Med 36:2225–2231. doi: 10.1097/CCM.0b013e31817b8a92 CrossRefPubMedGoogle Scholar
  28. 28.
    Futier E, Constantin J-M, Paugam-Burtz C et al (2013) A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med 369:428–437. doi: 10.1056/NEJMoa1301082 CrossRefPubMedGoogle Scholar
  29. 29.
    PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology, Hemmes SNT, Gama de Abreu M et al (2014) High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet 384:495–503. doi: 10.1016/S0140-6736(14)60416-5 CrossRefGoogle Scholar
  30. 30.
    Mascia L, Grasso S, Fiore T et al (2005) Cerebro-pulmonary interactions during the application of low levels of positive end-expiratory pressure. Intensive Care Med 31:373–379. doi: 10.1007/s00134-004-2491-2 CrossRefPubMedGoogle Scholar
  31. 31.
    Epstein SK (2002) Decision to extubate. Intensive Care Med 28:535–546. doi: 10.1007/s00134-002-1268-8 CrossRefPubMedGoogle Scholar
  32. 32.
    Godet T, Chabanne R, Marin J et al (2017) Extubation failure in brain-injured patients: risk factors and development of a prediction score in a preliminary prospective cohort study. Anesthesiology 126:104–114. doi: 10.1097/ALN.0000000000001379 CrossRefPubMedGoogle Scholar
  33. 33.
    Ferrer R, Artigas A, Levy MM et al (2008) Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA 299:2294–2303. doi: 10.1001/jama.299.19.2294 CrossRefPubMedGoogle Scholar
  34. 34.
    Sierra R, Benítez E, León C, Rello J (2005) Prevention and diagnosis of ventilator-associated pneumonia: a survey on current practices in Southern Spanish ICUs. Chest 128:1667–1673. doi: 10.1378/chest.128.3.1667 CrossRefPubMedGoogle Scholar
  35. 35.
    Bellani G, Laffey JG, Pham T et al (2016) Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 315:788–790. doi: 10.1001/jama.2016.0291 CrossRefPubMedGoogle Scholar
  36. 36.
    Zhu B, Li Z, Jiang L et al (2015) Effect of a quality improvement program on weaning from mechanical ventilation: a cluster randomized trial. Intensive Care Med 41:1781–1790. doi: 10.1007/s00134-015-3958-z CrossRefPubMedGoogle Scholar
  37. 37.
    Rhodes A, Phillips G, Beale R et al (2015) The surviving sepsis campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study). Intensive Care Med 41:1620–1628. doi: 10.1007/s00134-015-3906-y CrossRefPubMedGoogle Scholar
  38. 38.
    Kizer JR, Cannon CP, McCabe CH et al (1999) Trends in the use of pharmacotherapies for acute myocardial infarction among physicians who design and/or implement randomized trials versus physicians in routine clinical practice: the MILIS-TIMI experience. Multicenter investigation on limitation of infarct size. Thrombolysis in myocardial infarction. Am Heart J 137:79–92CrossRefPubMedGoogle Scholar
  39. 39.
    Bouadma L, Mourvillier B, Deiler V et al (2010) Changes in knowledge, beliefs, and perceptions throughout a multifaceted behavioral program aimed at preventing ventilator-associated pneumonia. Intensive Care Med 36:1341–1347. doi: 10.1007/s00134-010-1890-9 CrossRefPubMedGoogle Scholar
  40. 40.
    Bouadma L, Mourvillier B, Deiler V et al (2010) A multifaceted program to prevent ventilator-associated pneumonia: impact on compliance with preventive measures. Crit Care Med 38:789–796. doi: 10.1097/CCM.0b013e3181ce21af CrossRefPubMedGoogle Scholar
  41. 41.
    Klompas M (2010) Ventilator-associated pneumonia: is zero possible? Clin Infect Dis 51:1123–1126. doi: 10.1086/656738 CrossRefPubMedGoogle Scholar
  42. 42.
    Lilly CM, Cody S, Zhao H et al (2011) Hospital mortality, length of stay, and preventable complications among critically ill patients before and after tele-ICU reengineering of critical care processes. JAMA 305:2175–2183. doi: 10.1001/jama.2011.697 CrossRefPubMedGoogle Scholar
  43. 43.
    Concato J, Shah N, Horwitz RI (2000) Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 342:1887–1892. doi: 10.1056/NEJM200006223422507 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2017

Authors and Affiliations

  • Karim Asehnoune
    • 1
    • 20
    Email author
  • Ségolène Mrozek
    • 2
  • Pierre François Perrigault
    • 3
  • Philippe Seguin
    • 4
  • Claire Dahyot-Fizelier
    • 5
  • Sigismond Lasocki
    • 6
  • Anne Pujol
    • 7
  • Mathieu Martin
    • 8
  • Russel Chabanne
    • 9
  • Laurent Muller
    • 10
  • Jean Luc Hanouz
    • 11
  • Emmanuelle Hammad
    • 12
  • Bertrand Rozec
    • 13
  • Thomas Kerforne
    • 14
  • Carole Ichai
    • 15
  • Raphael Cinotti
    • 1
  • Thomas Geeraerts
    • 2
  • Djillali Elaroussi
    • 7
  • Paolo Pelosi
    • 16
  • Samir Jaber
    • 17
  • Marie Dalichampt
    • 18
  • Fanny Feuillet
    • 19
  • Véronique Sebille
    • 18
    • 19
  • Antoine Roquilly
    • 1
  • The BI-VILI study group
  1. 1.Intensive Care Unit, Anesthesia and Critical Care Department, Hôtel Dieu-HME–University Hospital of Nantes Centre Hospitalier Universitaire (CHU) de NantesNantesFrance
  2. 2.Department of Anesthesiology and Critical Care DepartmentUniversity Hospital of ToulouseToulouseFrance
  3. 3.Intensive Care Unit, Anesthesia and Critical Care DepartmentGui Chauliac University Hospital of MontpellierMontpellierFrance
  4. 4.Intensive Care Unit, Anesthesia and Critical Care DepartmentPontchaillou–University Hospital of RennesRennesFrance
  5. 5.Neuro-Intensive Care Unit, Anesthesia and Critical Care DepartmentUniversity Hospital of PoitiersPoitiersFrance
  6. 6.Intensive Care Unit, Anesthesia and Critical Care DepartmentUniversity Hospital of AngersAngersFrance
  7. 7.Intensive Care Unit, Anesthesia and Critical Care DepartmentUniversity Hospital of ToursToursFrance
  8. 8.Intensive Care Unit, Anesthesia and Critical Care Department, University Hospital of Créteil–CHU Henri MondorAssistance publique–Hôpitaux de Paris (AP-HP)CréteilFrance
  9. 9.Department of Anesthesiology and Intensive CareUniversity Hospital of Clermont FerrandClermont FerrandFrance
  10. 10.Department of Anesthesiology and Intensive CareUniversity Hospital of NimesNimesFrance
  11. 11.Department of Anesthesiology and Intensive CareUniversity Hospital of CaenCaenFrance
  12. 12.Department of Anesthesiology and Intensive CareUniversity Hospital of MarseilleMarseilleFrance
  13. 13.Intensive Care Unit, Anesthesia and Critical Care DepartmentLaennec–University Hospital of NantesNantesFrance
  14. 14.Surgical Intensive Care Unit, Anesthesia and Critical Care DepartmentUniversity Hospital of PoitiersPoitiersFrance
  15. 15.Intensive Care Unit Pasteur 2–University Hospital of NiceNiceFrance
  16. 16.Department of Surgical Sciences and Integrated Diagnostics, IRCCS AOU San Martino–IST National Cancer Research InstituteUniversity of GenoaGenoaItaly
  17. 17.Intensive Care Unit, Anesthesia and Critical Care DepartmentSaint Eloi University Hospital of MontpellierMontpellierFrance
  18. 18.Plateforme de Biométrie, Département Promotion de la Recherche CliniqueUniversity Hospital of NantesNantesFrance
  19. 19.EA 4275, MethodS for Patients-centered Outcomes and HEalth REsearch (SPHERE), UFR des Sciences PharmaceutiquesNantes UniversityNantesFrance
  20. 20.Service d’Anesthésie RéanimationCHU de NantesNantes Cedex 1France

Personalised recommendations