Biological markers of lung injury before and after the institution of positive pressure ventilation in patients with acute lung injury.
BACKGROUND
Several biological markers of lung injury are predictors of morbidity and mortality in patients with acute lung injury (ALI). The low tidal volume lung-protective ventilation strategy is associated with a significant decrease in plasma biomarker levels compared to the high tidal volume ventilation strategy. The primary objective of this study was to test whether the institution of lung-protective positive pressure ventilation in spontaneously ventilating patients with ALI exacerbates pre-existing lung injury by using measurements of biomarkers of lung injury before and after intubation.


METHODS
A prospective observational cohort study was conducted in the intensive care unit of a tertiary care university hospital. Twenty-five intubated, mechanically ventilated patients with ALI were enrolled. Physiologic data and serum samples were collected within 6 hours before intubation and at two different time points within the first 24 hours after intubation to measure the concentration of interleukin (IL)-6, IL-8, intercellular adhesion molecule 1 (ICAM-1), and von Willebrand factor (vWF). The differences in biomarker levels before and after intubation were analysed using repeated measures analysis of variance and a paired t test with correction for multiple comparisons.


RESULTS
Before endotracheal intubation, all of the biological markers (IL-8, IL-6, ICAM-1, and vWF) were elevated in the spontaneously breathing patients with ALI. After intubation and the institution of positive pressure ventilation (tidal volume 7 to 8 ml/kg per ideal body weight), none of the biological markers was significantly increased at either an early (3 +/- 2 hours) or later (21 +/- 5 hours) time point. However, the levels of IL-8 were significantly decreased at the later time point (21 +/- 5 hours) after intubation. During the 24-hour period after intubation, the PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio significantly increased and the plateau airway pressure significantly decreased.


CONCLUSIONS
Levels of IL-8, IL-6, vWF, and ICAM-1 are elevated in spontaneously ventilating patients with ALI prior to endotracheal intubation. The institution of a lung-protective ventilation strategy with positive pressure ventilation does not further increase the levels of biological markers of lung injury. The results suggest that the institution of a lung-protective positive pressure ventilation strategy does not worsen the pre-existing lung injury in most patients with ALI.
Cepkova
Magda
M
The Cardiovascular Research Institute and the Departments of Medicine and Anesthesia, University of California, San Francisco, 505 Parnassus Avenue, M917, San Francisco, CA 94143-0624, USA. magdac72@yahoo.com
Brady
Sandra
S
Sapru
Anil
A
Matthay
Michael A
MA
Church
Gwynne
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000503:physiopathology*; D013997:Time Factors
D015415:Biomarkers; D016207:Cytokines