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

Determann RM, Royakkers A, Wolthuis EK, Vlaar AP, Choi G, Paulus F, Hofstra JJ, de Graaff MJ, Korevaar JC, Schultz MJ - Crit Care (2010)

Bottom Line: 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)).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Intensive Care Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. r.m.determann@amc.uva.nl

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.

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Related in: MedlinePlus

Flow diagram summarizing inclusion, allocation, and analysis. 347 patients were eligible for the study; 94 patients were excluded because of participation in another clinical trial (n = 49), use of immunosuppressive agents (n = 22), chronic obstructive pulmonary disease (n = 11), prior pneumectomy or lobectomy (n = 5), interstitial lung disease (n = 4), and pulmonary thromboembolism (n = 3); 93 patients refused informed consent, and in eight patients, participation in the trial was denied by the attending physician.
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Figure 1: Flow diagram summarizing inclusion, allocation, and analysis. 347 patients were eligible for the study; 94 patients were excluded because of participation in another clinical trial (n = 49), use of immunosuppressive agents (n = 22), chronic obstructive pulmonary disease (n = 11), prior pneumectomy or lobectomy (n = 5), interstitial lung disease (n = 4), and pulmonary thromboembolism (n = 3); 93 patients refused informed consent, and in eight patients, participation in the trial was denied by the attending physician.

Mentions: A flow diagram summarizing patient inclusion, allocation, and analysis is given in Figure 1. At the second interim analysis, after 150 patients were included, the trial was stopped because more patients had developed lung injury in the conventional tidal-volume group as compared with the lower tidal-volume group ((10 patients (13.5%) versus two patients (2.6%); P = 0.01)). Demographics and admission diagnoses are shown in Tables 1 and 2. Study groups were well balanced with respect to the number of patients with P/F less than 40 kPa and unilateral chest radiographs abnormalities, the number of patients with bilateral chest radiographs abnormalities but P/F more than 40 kPa, and risk factors for ALI/ARDS. Patients randomized to the lower-tidal-volume group, however, tended to be older, and more patients were chronic smokers.


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

Determann RM, Royakkers A, Wolthuis EK, Vlaar AP, Choi G, Paulus F, Hofstra JJ, de Graaff MJ, Korevaar JC, Schultz MJ - Crit Care (2010)

Flow diagram summarizing inclusion, allocation, and analysis. 347 patients were eligible for the study; 94 patients were excluded because of participation in another clinical trial (n = 49), use of immunosuppressive agents (n = 22), chronic obstructive pulmonary disease (n = 11), prior pneumectomy or lobectomy (n = 5), interstitial lung disease (n = 4), and pulmonary thromboembolism (n = 3); 93 patients refused informed consent, and in eight patients, participation in the trial was denied by the attending physician.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875503&req=5

Figure 1: Flow diagram summarizing inclusion, allocation, and analysis. 347 patients were eligible for the study; 94 patients were excluded because of participation in another clinical trial (n = 49), use of immunosuppressive agents (n = 22), chronic obstructive pulmonary disease (n = 11), prior pneumectomy or lobectomy (n = 5), interstitial lung disease (n = 4), and pulmonary thromboembolism (n = 3); 93 patients refused informed consent, and in eight patients, participation in the trial was denied by the attending physician.
Mentions: A flow diagram summarizing patient inclusion, allocation, and analysis is given in Figure 1. At the second interim analysis, after 150 patients were included, the trial was stopped because more patients had developed lung injury in the conventional tidal-volume group as compared with the lower tidal-volume group ((10 patients (13.5%) versus two patients (2.6%); P = 0.01)). Demographics and admission diagnoses are shown in Tables 1 and 2. Study groups were well balanced with respect to the number of patients with P/F less than 40 kPa and unilateral chest radiographs abnormalities, the number of patients with bilateral chest radiographs abnormalities but P/F more than 40 kPa, and risk factors for ALI/ARDS. Patients randomized to the lower-tidal-volume group, however, tended to be older, and more patients were chronic smokers.

Bottom Line: 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)).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Intensive Care Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. r.m.determann@amc.uva.nl

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.

Show MeSH
Related in: MedlinePlus