Intensive Care Medicine

, Volume 43, Issue 2, pp 200–208 | Cite as

Severe hypercapnia and outcome of mechanically ventilated patients with moderate or severe acute respiratory distress syndrome

  • Nicolas Nin
  • Alfonso Muriel
  • Oscar Peñuelas
  • Laurent Brochard
  • José Angel Lorente
  • Niall D. Ferguson
  • Konstantinos Raymondos
  • Fernando Ríos
  • Damian A. Violi
  • Arnaud W. Thille
  • Marco González
  • Asisclo J. Villagomez
  • Javier Hurtado
  • Andrew R. Davies
  • Bin Du
  • Salvatore M. Maggiore
  • Luis Soto
  • Gabriel D’Empaire
  • Dimitrios Matamis
  • Fekri Abroug
  • Rui P. Moreno
  • Marco Antonio Soares
  • Yaseen Arabi
  • Freddy Sandi
  • Manuel Jibaja
  • Pravin Amin
  • Younsuck Koh
  • Michael A. Kuiper
  • Hans-Henrik Bülow
  • Amine Ali Zeggwagh
  • Antonio Anzueto
  • Jacob I. Sznajder
  • Andres EstebanEmail author
  • for the VENTILA Group



To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS).

Patients and methods

We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality.

Main outcomes

We included 1899 patients with ARDS in this study. The relationship between maximum PaCO2 in the first 48 h and mortality suggests higher mortality at or above PaCO2 of ≥50 mmHg. Patients with severe hypercapnia (PaCO2 ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO2/FiO2 ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04–2.41; p = 0.032).


Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.

Trial registration identifier, NCT01093482.


Mechanical ventilation Acute respiratory distress syndrome Hypercapnia ICU mortality 



Funding for this study was provided by CIBER Enfermedades Respiratorias (CIBERES), CIBER en Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain and the Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain. Dr. Ferguson was supported by a Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada). Dr. Sznajder is funded by HL-048129, HL-071643 and HL-085534.

Compliance with ethical standards

The funding organizations had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, and approval of the manuscript.

Supplementary material

134_2016_4611_MOESM1_ESM.docx (370 kb)
Supplementary material 1 (DOCX 369 kb)
134_2016_4611_MOESM2_ESM.docx (32 kb)
Supplementary material 2 (DOCX 32 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2017

Authors and Affiliations

  • Nicolas Nin
    • 1
    • 13
  • Alfonso Muriel
    • 2
  • Oscar Peñuelas
    • 3
    • 33
  • Laurent Brochard
    • 4
    • 5
  • José Angel Lorente
    • 3
    • 33
  • Niall D. Ferguson
    • 6
  • Konstantinos Raymondos
    • 7
  • Fernando Ríos
    • 8
  • Damian A. Violi
    • 9
  • Arnaud W. Thille
    • 10
  • Marco González
    • 11
  • Asisclo J. Villagomez
    • 12
  • Javier Hurtado
    • 13
  • Andrew R. Davies
    • 14
  • Bin Du
    • 15
  • Salvatore M. Maggiore
    • 16
  • Luis Soto
    • 17
  • Gabriel D’Empaire
    • 18
  • Dimitrios Matamis
    • 19
  • Fekri Abroug
    • 20
  • Rui P. Moreno
    • 21
  • Marco Antonio Soares
    • 22
  • Yaseen Arabi
    • 23
  • Freddy Sandi
    • 24
  • Manuel Jibaja
    • 25
  • Pravin Amin
    • 26
  • Younsuck Koh
    • 27
  • Michael A. Kuiper
    • 28
  • Hans-Henrik Bülow
    • 29
  • Amine Ali Zeggwagh
    • 30
  • Antonio Anzueto
    • 31
  • Jacob I. Sznajder
    • 32
  • Andres Esteban
    • 3
    • 33
    Email author
  • for the VENTILA Group
  1. 1.Hospital de TorrejónMadridSpain
  2. 2.Department of Clinical BiostatisticsHospital Ramón Y Cajal, IRICYS and CIBERESPMadridSpain
  3. 3.CIBER Enfermedades RespiratoriasMadridSpain
  4. 4.Keenan Research Centre, Li Ka Shing Knowledge InstituteSt Michael’s HospitalTorontoCanada
  5. 5.Interdepartmental Division of Critical Care MedicineUniversity of TorontoTorontoCanada
  6. 6.Interdepartmental Division of Critical Care Medicine and Departments of Medicine and PhysiologyUniversity of TorontoTorontoCanada
  7. 7.Medizinische Hochschule HannoverHanoverGermany
  8. 8.Hospital Nacional Alejandro PosadasBuenos AiresArgentina
  9. 9.Hospital HIGA GuemesHaedoArgentina
  10. 10.University Hospital of PoitiersPoitiersFrance
  11. 11.Clínica Medellín and Universidad Pontificia BolivarianaMedellínColombia
  12. 12.Hospital Regional 1° de Octubre, ISSSTEMexico CityMexico
  13. 13.Hospital EspañolMontevideoUruguay
  14. 14.Alfred Hospital and Monash UniversityMelbourneAustralia
  15. 15.Peking Union Medical College HospitalBeijingPeople’s Republic of China
  16. 16.Policlinico Agostino GemelliUniversità Cattolica Del Sacro CuoreRomeItaly
  17. 17.Instituto Nacional del Tórax de SantiagoSantiagoChile
  18. 18.Hospital de Clínicas de CaracasCaracasVenezuela
  19. 19.Papageorgiou HospitalThessalonikiGreece
  20. 20.Hospital Fattouma BourguinaMonastirTunisia
  21. 21.UCINC, Hospital de Sao JoséCentro Hospitalar de Lisboa Central, E.P.E.LisbonPortugal
  22. 22.Hospital Universitario Sao JoséBelo HorizonteBrazil
  23. 23.King Saud Bin Abdulaziz University for Health SciencesRiyadhSaudi Arabia
  24. 24.Hospital Obrero No. 1La PazBolivia
  25. 25.Hospital Eugenio EspejoQuitoEcuador
  26. 26.Bombay Hospital Institute of Medical SciencesMumbaiIndia
  27. 27.Asan Medical CenterUniversity of UlsanSeoulRepublic of Korea
  28. 28.Medical Center Leeuwarden (MCL)LeeuwardenThe Netherlands
  29. 29.Holbaek HospitalUniversity of CopenhagenCopenhagenDenmark
  30. 30.Hospital Ibn SinaRabatMorocco
  31. 31.South Texas Veterans Health Care System and University of Texas Health Science CenterSan AntonioUSA
  32. 32.Department of Medicine, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  33. 33.Hospital Universitario de GetafeCarretera de ToledoMadridSpain

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