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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

Serial data on cytokine levels in bronchoalveolar lavage fluid of patients ventilated with conventional tidal volume (solid circles) or lower tidal volumes (open circles). TNF-α = tumor necrosis factor-α; IL-1β = interleukin-1β; IL-6 = interleukin-6. The number of patients was 74 versus 76 (conventional versus lower tidal volumes), 55 versus 63, and 34 versus 34, respectively, at T = 0, T = 2, and T = 4 days. *P < 0.05; #P = 0.06 (Interaction time × Group).
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Figure 4: Serial data on cytokine levels in bronchoalveolar lavage fluid of patients ventilated with conventional tidal volume (solid circles) or lower tidal volumes (open circles). TNF-α = tumor necrosis factor-α; IL-1β = interleukin-1β; IL-6 = interleukin-6. The number of patients was 74 versus 76 (conventional versus lower tidal volumes), 55 versus 63, and 34 versus 34, respectively, at T = 0, T = 2, and T = 4 days. *P < 0.05; #P = 0.06 (Interaction time × Group).

Mentions: Baseline lavage-fluid levels of TNF-α and IL-1β were comparable in both study groups; baseline lavage-fluid levels of IL-6 were higher in the conventional group, although statistical significance was not reached ((384 (67 to 1,136) pg/ml versus 112 (20 to 548) pg/ml; P = 0.07)) (Figure 4). Lavage-fluid levels of cytokines remained comparable over time in both study groups. Baseline plasma IL-6 levels were comparable in both study groups ((50 (21 to 122) ng/ml versus 51 (20 to 182) ng/ml in the conventional- and lower-tidal-volume groups, respectively; P = 0.74)). In the conventional-tidal-volume group, plasma IL-6 levels decreased after 4 days ((21 (9 to 99) ng/ml)), but the decrease over time was more pronounced in the lower-tidal-volume group ((11 (5 to 20) ng/ml; P = 0.01)).


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)

Serial data on cytokine levels in bronchoalveolar lavage fluid of patients ventilated with conventional tidal volume (solid circles) or lower tidal volumes (open circles). TNF-α = tumor necrosis factor-α; IL-1β = interleukin-1β; IL-6 = interleukin-6. The number of patients was 74 versus 76 (conventional versus lower tidal volumes), 55 versus 63, and 34 versus 34, respectively, at T = 0, T = 2, and T = 4 days. *P < 0.05; #P = 0.06 (Interaction time × Group).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Serial data on cytokine levels in bronchoalveolar lavage fluid of patients ventilated with conventional tidal volume (solid circles) or lower tidal volumes (open circles). TNF-α = tumor necrosis factor-α; IL-1β = interleukin-1β; IL-6 = interleukin-6. The number of patients was 74 versus 76 (conventional versus lower tidal volumes), 55 versus 63, and 34 versus 34, respectively, at T = 0, T = 2, and T = 4 days. *P < 0.05; #P = 0.06 (Interaction time × Group).
Mentions: Baseline lavage-fluid levels of TNF-α and IL-1β were comparable in both study groups; baseline lavage-fluid levels of IL-6 were higher in the conventional group, although statistical significance was not reached ((384 (67 to 1,136) pg/ml versus 112 (20 to 548) pg/ml; P = 0.07)) (Figure 4). Lavage-fluid levels of cytokines remained comparable over time in both study groups. Baseline plasma IL-6 levels were comparable in both study groups ((50 (21 to 122) ng/ml versus 51 (20 to 182) ng/ml in the conventional- and lower-tidal-volume groups, respectively; P = 0.74)). In the conventional-tidal-volume group, plasma IL-6 levels decreased after 4 days ((21 (9 to 99) ng/ml)), but the decrease over time was more pronounced in the lower-tidal-volume group ((11 (5 to 20) ng/ml; P = 0.01)).

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