Skip to main content
Top
Published in: Critical Care 1/2010

Open Access 01-02-2010 | Research

Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial

Authors: Rogier M Determann, Annick Royakkers, Esther K Wolthuis, Alexander P Vlaar, Goda Choi, Frederique Paulus, Jorrit-Jan Hofstra, Mart J de Graaff, Johanna C Korevaar, Marcus J Schultz

Published in: Critical Care | Issue 1/2010

Login to get access

Abstract

Introduction

Recent cohort studies have identified the use of large tidal volumes as a major risk factor for development of lung injury in mechanically ventilated patients without acute lung injury (ALI). We compared the effect of conventional with lower tidal volumes on pulmonary inflammation and development of lung injury in critically ill patients without ALI at the onset of mechanical ventilation.

Methods

We performed a randomized controlled nonblinded preventive trial comparing mechanical ventilation with tidal volumes of 10 ml versus 6 ml per kilogram of predicted body weight in critically ill patients without ALI at the onset of mechanical ventilation. The primary end point was cytokine levels in bronchoalveolar lavage fluid and plasma during mechanical ventilation. The secondary end point was the development of lung injury, as determined by consensus criteria for ALI, duration of mechanical ventilation, and mortality.

Results

One hundred fifty patients (74 conventional versus 76 lower tidal volume) were enrolled and analyzed. No differences were observed in lavage fluid cytokine levels at baseline between the randomization groups. Plasma interleukin-6 (IL-6) levels decreased significantly more strongly in the lower-tidal-volume group ((from 51 (20 to 182) ng/ml to 11 (5 to 20) ng/ml versus 50 (21 to 122) ng/ml to 21 (20 to 77) ng/ml; P = 0.01)). The trial was stopped prematurely for safety reasons because the development of lung injury was higher in the conventional tidal-volume group as compared with the lower tidal-volume group (13.5% versus 2.6%; P = 0.01). Univariate analysis showed statistical relations between baseline lung-injury score, randomization group, level of positive end-expiratory pressure (PEEP), the number of transfused blood products, the presence of a risk factor for ALI, and baseline IL-6 lavage fluid levels and the development of lung injury. Multivariate analysis revealed the randomization group and the level of PEEP as independent predictors of the development of lung injury.

Conclusions

Mechanical ventilation with conventional tidal volumes is associated with sustained cytokine production, as measured in plasma. Our data suggest that mechanical ventilation with conventional tidal volumes contributes to the development of lung injury in patients without ALI at the onset of mechanical ventilation.

Trial registration

ISRCTN82533884
Appendix
Available only for authorised users
Literature
1.
go back to reference Dreyfuss D, Saumon G: Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 1998, 157: 294-323.CrossRefPubMed Dreyfuss D, Saumon G: Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 1998, 157: 294-323.CrossRefPubMed
2.
go back to reference Carney D, DiRocco J, Nieman G: Dynamic alveolar mechanics and ventilator-induced lung injury. Crit Care Med 2005, 33: S122-128. 10.1097/01.CCM.0000155928.95341.BCCrossRefPubMed Carney D, DiRocco J, Nieman G: Dynamic alveolar mechanics and ventilator-induced lung injury. Crit Care Med 2005, 33: S122-128. 10.1097/01.CCM.0000155928.95341.BCCrossRefPubMed
3.
go back to reference Plotz FB, Slutsky AS, van Vught AJ, Heijnen CJ: Ventilator-induced lung injury and multiple system organ failure: a critical review of facts and hypotheses. Intensive Care Med 2004, 30: 1865-1872. 10.1007/s00134-004-2363-9CrossRefPubMed Plotz FB, Slutsky AS, van Vught AJ, Heijnen CJ: Ventilator-induced lung injury and multiple system organ failure: a critical review of facts and hypotheses. Intensive Care Med 2004, 30: 1865-1872. 10.1007/s00134-004-2363-9CrossRefPubMed
4.
go back to reference Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome: the Acute Respiratory Distress Syndrome Network N Engl J Med 2000, 342: 1301-1308. 10.1056/NEJM200005043421801 Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome: the Acute Respiratory Distress Syndrome Network N Engl J Med 2000, 342: 1301-1308. 10.1056/NEJM200005043421801
5.
go back to reference 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: Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998, 338: 347-354. 10.1056/NEJM199802053380602CrossRefPubMed 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: Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998, 338: 347-354. 10.1056/NEJM199802053380602CrossRefPubMed
6.
go back to reference Villar J, Kacmarek RM, Perez-Mendez L, Aguirre-Jaime A, for the ARIES Network: A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med 2006, 34: 1311-1318. 10.1097/01.CCM.0000215598.84885.01CrossRefPubMed Villar J, Kacmarek RM, Perez-Mendez L, Aguirre-Jaime A, for the ARIES Network: A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial. Crit Care Med 2006, 34: 1311-1318. 10.1097/01.CCM.0000215598.84885.01CrossRefPubMed
7.
go back to reference Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM: Surviving Sepsis Campaign Management Guidelines Committee: surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36: 296-327. 10.1097/01.CCM.0000298158.12101.41CrossRefPubMed Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM: Surviving Sepsis Campaign Management Guidelines Committee: surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36: 296-327. 10.1097/01.CCM.0000298158.12101.41CrossRefPubMed
8.
go back to reference Schultz MJ, Haitsma JJ, Slutsky AS, Gajic O: What tidal volumes should be used in patients without ALI/ARDS? Anesthesiology 2007, 106: 1226-1231. 10.1097/01.anes.0000267607.25011.e8CrossRefPubMed Schultz MJ, Haitsma JJ, Slutsky AS, Gajic O: What tidal volumes should be used in patients without ALI/ARDS? Anesthesiology 2007, 106: 1226-1231. 10.1097/01.anes.0000267607.25011.e8CrossRefPubMed
9.
go back to reference Hudson LD, Milberg JA, Anardi D, Maunder RJ: Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med 1995, 151: 293-301.CrossRefPubMed Hudson LD, Milberg JA, Anardi D, Maunder RJ: Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med 1995, 151: 293-301.CrossRefPubMed
10.
go back to reference Stewart TE, Meade MO, Cook DJ, Granton JT, Hodder RV, Lapinsky SE, Mazer CD, McLean RF, Rogovein TS, Schouten BD, Todd TRJ, Slutsky AS: Evaluation of a ventilation strategy to prevent barotraumas in patients at high risk for acute respiratory distress syndrome. N Engl J Med 1998, 338: 355-361. 10.1056/NEJM199802053380603CrossRefPubMed Stewart TE, Meade MO, Cook DJ, Granton JT, Hodder RV, Lapinsky SE, Mazer CD, McLean RF, Rogovein TS, Schouten BD, Todd TRJ, Slutsky AS: Evaluation of a ventilation strategy to prevent barotraumas in patients at high risk for acute respiratory distress syndrome. N Engl J Med 1998, 338: 355-361. 10.1056/NEJM199802053380603CrossRefPubMed
11.
go back to reference Choi G, Wolthuis EK, Bresser P, Levi M, Poll T, Dzoljic M, Vroom MB, Schultz MJ: Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents alveolar coagulation in patients without acute lung injury. Anesthesiology 2006, 105: 689-695. 10.1097/00000542-200610000-00013CrossRefPubMed Choi G, Wolthuis EK, Bresser P, Levi M, Poll T, Dzoljic M, Vroom MB, Schultz MJ: Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents alveolar coagulation in patients without acute lung injury. Anesthesiology 2006, 105: 689-695. 10.1097/00000542-200610000-00013CrossRefPubMed
12.
go back to reference Michelet P, D'Journo XB, Roch A, Doddoli C, Marin V, Papazian L, Decamps I, Bregeon F, Thomas P, Auffray JP: Protective ventilation influences systemic inflammation after esophagectomy: a randomized controlled study. Anesthesiology 2006, 105: 911-919. 10.1097/00000542-200611000-00011CrossRefPubMed Michelet P, D'Journo XB, Roch A, Doddoli C, Marin V, Papazian L, Decamps I, Bregeon F, Thomas P, Auffray JP: Protective ventilation influences systemic inflammation after esophagectomy: a randomized controlled study. Anesthesiology 2006, 105: 911-919. 10.1097/00000542-200611000-00011CrossRefPubMed
13.
go back to reference Wrigge H, Uhlig U, Baumgarten G, Menzenbach J, Zinserling J, Ernst M, Dromann D, Welz A, Uhlig S, Putensen C: Mechanical ventilation strategies and inflammatory responses to cardiac surgery: a prospective randomized clinical trial. Intensive Care Med 2005, 31: 1379-1387. 10.1007/s00134-005-2767-1CrossRefPubMed Wrigge H, Uhlig U, Baumgarten G, Menzenbach J, Zinserling J, Ernst M, Dromann D, Welz A, Uhlig S, Putensen C: Mechanical ventilation strategies and inflammatory responses to cardiac surgery: a prospective randomized clinical trial. Intensive Care Med 2005, 31: 1379-1387. 10.1007/s00134-005-2767-1CrossRefPubMed
14.
go back to reference Wrigge H, Uhlig U, Zinserling J, Behrends-Callsen E, Ottersbach G, Fischer M, Uhlig S, Putensen C: The effects of different ventilatory settings on pulmonary and systemic inflammatory responses during major surgery. Anesth Analg 2004, 98: 775-781. 10.1213/01.ANE.0000100663.11852.BFCrossRefPubMed Wrigge H, Uhlig U, Zinserling J, Behrends-Callsen E, Ottersbach G, Fischer M, Uhlig S, Putensen C: The effects of different ventilatory settings on pulmonary and systemic inflammatory responses during major surgery. Anesth Analg 2004, 98: 775-781. 10.1213/01.ANE.0000100663.11852.BFCrossRefPubMed
15.
go back to reference Gajic O, Dara SI, Mendez JL, Adesanya AO, Festic E, Caples SM, Rana R, St Sauver JL, Lymp JF, Afessa B, Hubmayr RD: Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med 2004, 32: 1817-1824. 10.1097/01.CCM.0000133019.52531.30CrossRefPubMed Gajic O, Dara SI, Mendez JL, Adesanya AO, Festic E, Caples SM, Rana R, St Sauver JL, Lymp JF, Afessa B, Hubmayr RD: Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med 2004, 32: 1817-1824. 10.1097/01.CCM.0000133019.52531.30CrossRefPubMed
16.
go back to reference Gajic O, Frutos-Vivar F, Esteban A, Hubmayr RD, Anzueto A: Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients. Intensive Care Med 2005, 31: 922-926. 10.1007/s00134-005-2625-1CrossRefPubMed Gajic O, Frutos-Vivar F, Esteban A, Hubmayr RD, Anzueto A: Ventilator settings as a risk factor for acute respiratory distress syndrome in mechanically ventilated patients. Intensive Care Med 2005, 31: 922-926. 10.1007/s00134-005-2625-1CrossRefPubMed
17.
go back to reference Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R: The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994, 149: 818-824.CrossRefPubMed Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R: The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994, 149: 818-824.CrossRefPubMed
18.
go back to reference Trachsel D, McCrindle BW, Nakagawa S, Bohn D: Oxygenation index predicts outcome in children with acute hypoxemic respiratory failure. Am J Respir Crit Care Med 2005, 172: 206-211. 10.1164/rccm.200405-625OCCrossRefPubMed Trachsel D, McCrindle BW, Nakagawa S, Bohn D: Oxygenation index predicts outcome in children with acute hypoxemic respiratory failure. Am J Respir Crit Care Med 2005, 172: 206-211. 10.1164/rccm.200405-625OCCrossRefPubMed
19.
go back to reference Millo JL, Schultz MJ, Williams C, Weverling GJ, Ringrose T, Mackinlay CI, Poll T, Garrard CS: Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia. Intensive Care Med 2004, 30: 68-74. 10.1007/s00134-003-2060-0CrossRefPubMed Millo JL, Schultz MJ, Williams C, Weverling GJ, Ringrose T, Mackinlay CI, Poll T, Garrard CS: Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia. Intensive Care Med 2004, 30: 68-74. 10.1007/s00134-003-2060-0CrossRefPubMed
20.
go back to reference Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003, 31: 1250-1256. 10.1097/01.CCM.0000050454.01978.3BCrossRefPubMed Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003, 31: 1250-1256. 10.1097/01.CCM.0000050454.01978.3BCrossRefPubMed
22.
go back to reference Thakur L, Kojicic M, Thakur SJ, Pieper MS, Kashyap R, Trillo-Alvarez CA, Javier F, Cartin-Ceba R, Gajic O: Alcohol consumption and development of acute respiratory distress syndrome: a population-based study. Int J Environ Res Public Health 2009, 6: 2426-2435. 10.3390/ijerph6092426PubMedCentralCrossRefPubMed Thakur L, Kojicic M, Thakur SJ, Pieper MS, Kashyap R, Trillo-Alvarez CA, Javier F, Cartin-Ceba R, Gajic O: Alcohol consumption and development of acute respiratory distress syndrome: a population-based study. Int J Environ Res Public Health 2009, 6: 2426-2435. 10.3390/ijerph6092426PubMedCentralCrossRefPubMed
23.
go back to reference Ranieri VM, Suter PM, Tortorella C, de Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS: Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 1999, 282: 54-61. 10.1001/jama.282.1.54CrossRefPubMed Ranieri VM, Suter PM, Tortorella C, de Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS: Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 1999, 282: 54-61. 10.1001/jama.282.1.54CrossRefPubMed
24.
go back to reference Iscimen R, Cartin-Ceba R, Yilmaz M, Khan H, Hubmayr RD, Afessa B, Gajic O: Risk factors for the development of acute lung injury in patients with septic shock: an observational cohort study. Crit Care Med 2008, 36: 1518-1522. 10.1097/CCM.0b013e31816fc2c0CrossRefPubMed Iscimen R, Cartin-Ceba R, Yilmaz M, Khan H, Hubmayr RD, Afessa B, Gajic O: Risk factors for the development of acute lung injury in patients with septic shock: an observational cohort study. Crit Care Med 2008, 36: 1518-1522. 10.1097/CCM.0b013e31816fc2c0CrossRefPubMed
25.
go back to reference Yilmaz M, Keegan MT, Iscimen R, Afessa B, Buck CF, Hubmayr RD, Gajic O: Toward the prevention of acute lung injury: protocol-guided limitation of large tidal volume ventilation and inappropriate transfusion. Crit Care Med 2007, 35: 1660-1666. 10.1097/01.CCM.0000269037.66955.F0CrossRefPubMed Yilmaz M, Keegan MT, Iscimen R, Afessa B, Buck CF, Hubmayr RD, Gajic O: Toward the prevention of acute lung injury: protocol-guided limitation of large tidal volume ventilation and inappropriate transfusion. Crit Care Med 2007, 35: 1660-1666. 10.1097/01.CCM.0000269037.66955.F0CrossRefPubMed
26.
go back to reference Ferguson ND, Frutos-Vivar F, Esteban A, Fernández-Segoviano P, Aramburu JA, Nájera L, Stewart TE: Acute respiratory distress syndrome: underrecognition by clinicians and diagnostic accuracy of three clinical definitions. Crit Care Med 2005, 33: 2228-2234. 10.1097/01.CCM.0000181529.08630.49CrossRefPubMed Ferguson ND, Frutos-Vivar F, Esteban A, Fernández-Segoviano P, Aramburu JA, Nájera L, Stewart TE: Acute respiratory distress syndrome: underrecognition by clinicians and diagnostic accuracy of three clinical definitions. Crit Care Med 2005, 33: 2228-2234. 10.1097/01.CCM.0000181529.08630.49CrossRefPubMed
27.
go back to reference Fartoukh M, Maitre B, Honore S, Cerf C, Zahar JR, Brun-Buisson C: Diagnosing pneumonia during mechanical ventilation: the clinical pulmonary infection score revisited. Am J Respir Crit Care Med 2003, 168: 173-179. 10.1164/rccm.200212-1449OCCrossRefPubMed Fartoukh M, Maitre B, Honore S, Cerf C, Zahar JR, Brun-Buisson C: Diagnosing pneumonia during mechanical ventilation: the clinical pulmonary infection score revisited. Am J Respir Crit Care Med 2003, 168: 173-179. 10.1164/rccm.200212-1449OCCrossRefPubMed
Metadata
Title
Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial
Authors
Rogier M Determann
Annick Royakkers
Esther K Wolthuis
Alexander P Vlaar
Goda Choi
Frederique Paulus
Jorrit-Jan Hofstra
Mart J de Graaff
Johanna C Korevaar
Marcus J Schultz
Publication date
01-02-2010
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2010
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc8230

Other articles of this Issue 1/2010

Critical Care 1/2010 Go to the issue