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 Esteban
  • for the VENTILA Group
Original

Abstract

Purpose

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).

Conclusions

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

Trial registration

Clinicaltrials.gov identifier, NCT01093482.

Keywords

Mechanical ventilation Acute respiratory distress syndrome Hypercapnia ICU mortality 

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)

References

  1. 1.
    Webb H, Tierney DF (1974) Experimental pulmonary edema due to intermittent positive pressure ventilation with high tidal inflation pressures. Am Rev Respir Dis 110:556–565PubMedGoogle Scholar
  2. 2.
    Dreyfuss D, Soler P, Basset G, Saumon G (1988) High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 137:1159–1164CrossRefPubMedGoogle Scholar
  3. 3.
    Corbridge TC, Wood LD, Crawford GP, Chudoba MJ, Yanos J, Sznajder JI (1990) Adverse effects of large tidal volume and low PEEP in canine acid aspiration. Am Rev Respir Dis 142:311–315CrossRefPubMedGoogle Scholar
  4. 4.
    Hickling KG, Henderson SJ, Jackson R (1990) Low mortality associated with low volume pressure limited ventilation with permissive hypercapnia in severe adult respiratory distress syndrome. Intensive Care Med 16:372–377CrossRefPubMedGoogle Scholar
  5. 5.
    Stewart TE, Meade MO, Cook DJ, Stewart TE, Meade MO, Cook DJ, Pressure- and Volume-Limited Ventilation Strategy Group (1998) Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. N Engl J Med 338:355–361CrossRefPubMedGoogle Scholar
  6. 6.
    Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR (1998) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338:347–354CrossRefPubMedGoogle Scholar
  7. 7.
    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 342:1301–1308CrossRefGoogle Scholar
  8. 8.
    Broccard AF, Hotchkiss JR, Vannay C, Markert M, Sauty A, Feihl F, Schaller MD (2001) Protective effects of hypercapnic acidosis on ventilator-induced lung injury. Am J Respir Crit Care Med 22:802–806CrossRefGoogle Scholar
  9. 9.
    Sinclair SE, Kregenow DA, Lamm WJ, Starr IR, Chi EY, Hlastala MP (2002) Hypercapnic acidosis is protective in an in vivo model of ventilator-induced lung injury. Am J Respir Crit Care Med 166:403–408CrossRefPubMedGoogle Scholar
  10. 10.
    Feihl F, Perret C (1994) Permissive hypercapnia: how permissive should we be? Am J Respir Crit Care Med 150:1722–1737CrossRefPubMedGoogle Scholar
  11. 11.
    Laffey JG, Kavanagh BP (1999) Carbon dioxide and the critically ill—too little of a good thing? Lancet 354:1283–1286CrossRefPubMedGoogle Scholar
  12. 12.
    Laffey JG, Tanaka M, Engelberts D, Luo X, Yuan S, Tanswell AK, Post M, Lindsay T, Kavanagh BP (2000) Therapeutic hypercapnia reduces pulmonary and systemic injury following in vivo lung reperfusion. Am J Respir Crit Care Med 162:2287–2294CrossRefPubMedGoogle Scholar
  13. 13.
    Jaitovich A, Angulo M, Lecuona E, Dada LA, Welch LC, Cheng Y, Gusarova G, Ceco E, Liu C, Shigemura M, Barreiro E, Patterson C, Nader GA, Sznajder JI (2015) High CO2 levels cause skeletal muscle atrophy via AMP-activated kinase (AMPK), FoxO3a protein, and muscle-specific Ring finger protein 1 (MuRF1). J Biol Chem 290:9183–9194CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Briva A, Vadász I, Lecuona E, Welch LC, Chen J, Dada LA, Trejo HE, Dumasius V, Azzam ZS, Myrianthefs PM, Batlle D, Gruenbaum Y, Sznajder JI (2007) High CO2 levels impair alveolar epithelial function independently of pH. PLoS ONE 211:1238CrossRefGoogle Scholar
  15. 15.
    Doerr CH, Gajic O, Berrios JC, Caples S, Abdel M, Lymp JF, Hubmayr RD (2005) Hypercapnic acidosis impairs plasma membrane wound resealing in ventilator-injured lungs. Am J Respir Crit Care Med 171:1371–1377CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Helenius IT, Krupinski T, Turnbull DW, Gruenbaum Y, Silverman N, Johnson EA, Sporn PH, Sznajder JI, Beitel GJ (2009) Elevated CO2 suppresses specific drosophila innate immune responses and resistance to bacterial infection. Proc Natl Acad Sci USA 106:18710–18715CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Sharabi K, Hurwitz A, Simon AJ, Beitel GJ, Morimoto RI, Rechavi G, Sznajder JI, Gruenbaum Y (2009) Elevated CO2 levels affect development, motility, and fertility and extend life span in Caenorhabditis elegans. Proc Natl Acad Sci USA 106:4024–4029CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Vohwinkel CU, Lecuona E, Sun H, Sommer N, Vadász I, Chandel NS, Sznajder JI (2011) Hypercapnia leads to mitochondrial dysfunction and decreased cell proliferation. J Biol Chem 286:37067–37076CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Vadász I, Dada LA, Briva A, Helenius IT, Sharabi K, Welch LC, Kelly AM, Grzesik BA, Budinger GR, Liu J, Seeger W, Beitel GJ, Gruenbaum Y, Sznajder JI (2012) Evolutionary conserved role of c-Jun-N-terminal kinase in CO2-induced epithelial dysfunction. PLoS ONE 7:e46696CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gates KL, Howell HA, Nair A (2013) Hypercapnia impairs lung neutrophil function and increases mortality in murine Pseudomonas pneumonia. Am J Respir Cell Mol Biol 49:821–828CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Dada LA, Trejo Bittar HE, Welch LC, Vagin O, Deiss-Yehiely N, Kelly AM, Baker MR, Capri J, Cohn W, Whitelegge JP, Vadász I, Gruenbaum Y, Sznajder JI (2015) High CO2 leads to Na, K-ATPase endocytosis via c-Jun amino-terminal kinase-induced LMO7b phosphorylation. Mol Cell Biol 35:3962–3973CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Bharat A, Graf N, Mullen A, Kanter J, Andrei AC, Sporn PH, DeCamp MM, Sznajder JI (2016) Pleural hypercarbia after lung surgery is associated with persistent alveolo-pleural fistulae. Chest 149:220–227CrossRefPubMedGoogle Scholar
  23. 23.
    Esteban A, Anzueto A, Frutos F, Alía I, Brochard L, Stewart TE, Benito S, Epstein SK, Apezteguía C, Nightingale P, Arroliga AC, Tobin MJ, Mechanical Ventilation International Study Group (2002) Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA 287:345–355CrossRefPubMedGoogle Scholar
  24. 24.
    Esteban A, Ferguson ND, Meade MO, Frutos-Vivar F, Apezteguia C, Brochard L, Raymondos K, Nin N, Hurtado J et al (2008) Evolution of mechanical ventilation in response to clinical research. Am J Respir Crit Care Med 177:170–177CrossRefPubMedGoogle Scholar
  25. 25.
    Esteban A, Frutos-Vivar F, Muriel A, Ferguson ND, Peñuelas O, Abraira V, Raymondos K, Rios F, Nin N, Apezteguía C et al (2013) Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med 188:220–230CrossRefPubMedGoogle Scholar
  26. 26.
    Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet JF, Eisner MD, Matthay MA (2002) Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med 346:1281–1286CrossRefPubMedGoogle Scholar
  27. 27.
    Wexler HR, Lok P (1981) A simple formula for adjusting arterial carbon dioxide tension. Can Anaesth Soc J 28:370–372CrossRefPubMedGoogle Scholar
  28. 28.
    Rosenbaum P, Rubin D (1983) The central role of the propensity score in observational studies for causal effects. Biometrika 70:41–55CrossRefGoogle Scholar
  29. 29.
    Austin PC (2011) Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat 10:150–161CrossRefPubMedGoogle Scholar
  30. 30.
    Mariani G, Cifuentes J, Carlo WA (1999) Randomized trial of permissive hypercapnia in preterm infants. Pediatrics 104:1082–1088CrossRefPubMedGoogle Scholar
  31. 31.
    Kregenow DA, Rubenfeld GD, Hudson LD, Swenson ER (2006) Hypercapnic acidosis and mortality in acute lung injury. Crit Care Med 34:1–7CrossRefPubMedGoogle Scholar
  32. 32.
    Brown LM, Calfee CS, Matthay MA, Brower RG, Thompson BT, Checkley W, National Institutes of Health Acute Respiratory Distress Syndrome Network Investigators (2011) A simple classification model for hospital mortality in patients with acute lung injury managed with lung protective ventilation. Crit Care Med 39:2645–2651CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Laserna E, Sibila O, Aguilar PR, Mortensen EM, Anzueto A, Blanquer JM, Sanz F, Rello J, Marcos PJ, Velez MI, Aziz N, Restrepo MI (2012) Hypocapnia and hypercapnia are predictors for ICU admission and mortality in hospitalized patients with community-acquired pneumonia. Chest 142:1193–1199CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Schisterman EF, Cole SR, Platt RW (2009) Over adjustment bias and unnecessary adjustment in epidemiologic studies. Epidemiology 20:488–495CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Passalacqua KD, Varadarajan A, Byrd B, Bergman NH (2009) Comparative transcriptional profiling of Bacillus cereus sensu lato strains during growth in CO2-bicarbonate and aerobic atmospheres. PLoS ONE 4:e4904CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Sin DD, Man SF, Marrie TJ (2005) Arterial carbon dioxide tension on admission as a marker of in-hospital mortality in community-acquired pneumonia. Am J Med 118:145–150CrossRefPubMedGoogle Scholar
  37. 37.
    Granger DL, Perfect JR, Durack DT (1985) Virulence of Cryptococcus neoformans: regulation of capsule synthesis by carbon dioxide. J Clin Invest 76:508–516CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Mekontso Dessap A, Charron C, Devaquet J, Aboab J, Jardin F, Brochard L, Vieillard-Baron A (2009) Impact of acute hypercapnia and augmented positive end-expiratory pressure on right ventricle function in severe acute respiratory distress syndrome. Intensive Care Med 35:1850–1858CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Bull TM, Clark B, McFann K, Moss M (2010) Pulmonary vascular dysfunction is associated with poor outcomes in patients with acute lung injury. Am J Respir Crit Care Med 182:1123–1128CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Boissier F, Katsahian S, Razazi K, Thille AW, Roche-Campo F, Leon R, Vivier E, Brochard L, Vieillard-Baron A, Brun-Buisson C, Mekontso Dessap A (2013) Prevalence and prognosis of cor-pulmonale during protective ventilation for acute respiratory distress syndrome. Intensive Care Med 39:1725–1733CrossRefPubMedGoogle Scholar
  41. 41.
    Schmitt JM, Vieillard-Baron A, Augarde R, Prin S, Page B, Jardin F (2001) Acute cor pulmonale in acute respiratory distress syndrome submitted to protective ventilation: incidence, clinical implications, and prognosis. Crit Care Med 29:1551–1555CrossRefPubMedGoogle Scholar

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
  • 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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