Biological markers of lung injury before and after the institution of positive pressure ventilation in patients with acute lung injury

Abstract

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.

Materials and 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.

Conclusion: 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.

Figure 1

Boxplot summary of interleukin (IL)-8 levels (upper panel) and boxplot summary of log-transformed IL-8 levels to achieve normal distribution (lower panel). Median levels of IL-8 were 235 pg/ml (range, 10 to 1,836 pg/ml) pre-intubation, 219 pg/ml (range, 10 to 2,115 pg/ml) immediately post-intubation, and 68 pg/ml (range, 10 to 1,552 pg/ml) at 12 to 26 hours post-intubation. The mean levels of IL-8 after log transformation were 5.2 ± 1.8 pg/ml, 5.5 ± 1.5 pg/ml, and 4.5 ± 1.5 pg/ml, respectively. The decrease in IL-8 level at 12 to 26 hours after intubation was statistically significant (p = 0.002, paired t test with Bonferroni correction for multiple comparisons). The horizontal line represents the median, the box encompasses the 25^th to 75^th percentile, and error bars encompass the 10^th to 90^th percentile.

Figure 2

Boxplot summary of interleukin (IL)-6 levels (upper panel) and boxplot summary of log-transformed IL-6 levels to achieve normal distribution (lower panel). Median levels of IL-6 were 76 pg/ml (range, 3 to 652 pg/ml) pre-intubation, 132 pg/ml (range, 4 to 971 pg/ml) immediately post-intubation, and 90 pg/ml (range, 3 to 550 pg/ml) at 12 to 26 hours post-intubation. The mean levels of IL-6 after log transformation were 4.4 ± 1.5 pg/ml, 4.7 ± 1.4 pg/ml, and 4.2 ± 1.5 pg/ml, respectively. There was no difference among the levels of IL-6 at the three different time points (p = 0.34). The horizontal line represents the median, the box encompasses the 25^th to 75^th percentile, and error bars encompass the 10^th to 90^th percentile.

Figure 3

Boxplot summary of intercellular adhesion molecule-1 (ICAM-1) levels (upper panel) and boxplot summary of log-transformed ICAM-1 levels to achieve normal distribution (lower panel). Median levels of ICAM-1 were 631 ng/ml (range, 220 to 2,800 ng/ml) pre-intubation, 520 ng/ml (range, 198 to 3,970 ng/ml) immediately post-intubation, and 492 ng/ml (range, 221 to 1,780 ng/ml) at 12 to 26 hours post-intubation. The mean levels of ICAM-1 after log transformation were 6.5 ± 0.6 ng/ml, 6.3 ± 0.7 ng/ml, and 6.4 ± 0.6 ng/ml, respectively. There was no statistically significant difference among the levels of ICAM-1 at the three different time points (p = 0.15). The horizontal line represents the median, the box encompasses the 25^th to 75^th percentile, and error bars encompass the 10^th to 90^th percentile.

Figure 4

Boxplot summary of von Willebrand factor (vWF) levels expressed as a percentage of a normal pooled plasma control reference. Median levels of vWF were 368% (range, 116% to 742%) pre-intubation, 312% (range, 40% to 814%) immediately post-intubation, and 359% (range, 91% to 653%) at 12 to 26 hours post-intubation. There was no statistically significant difference among the levels of vWF at the three different time points (p = 0.57). The horizontal line represents the median, the box encompasses the 25^th to 75^th percentile, and error bars encompass the 10^th to 90^th percentile.