Ventilator-Induced Lung Injury in Children

DESCRIPTION (provided by applicant): The long-term goal of this research project is to develop ventilator strategies that will minimize lung damage in children thus leading to a decrease in mortality and chronic lung injury. The objective of this R21 application is to compare the extent of lung injury in children with two different ventilator strategies: pressure control and volume control ventilation. The central hypothesis for the proposed research is that compared to volume control, pressure control ventilation causes increased lung damage. Evidence of lung damage will be assessed by increase in oxygenation indices. Increase in concentrations of the pro-inflammatory cytokines tumor necrosis factor alpha, interleukin-6, and interleukin-8 will be used as indicators of injury. We have formulated this hypothesis based on strong preliminary findings from pre-clinical data in rats with acute lung injury. These data demonstrate that pressure control ventilation is associated with higher oxygenation indices and increased production of the pro-inflammatory mediators, specifically; tumor necrosis factor, cytokine-induced neutrophil chemoattractant and macrophage inflammatory protein-2. The rationale for the proposed research is that human pediatric studies are essential to provide a rational basis for selection of ventilation mode for treatment of children with acute lung injury. In this pilot study, children with and without chronic lung disease who develop respiratory failure from acute lung injury will be randomized to receive either pressure or volume control ventilation. Children with chronic lung disease will be studied separately from children with no previous lung disease. Oxygenation indices and pro-inflammatory cytokine concentrations of tumor necrosis factor alpha, interleukin-6, and interleukin-8 will be measured daily in the blood and lung lavage fluid for the first three days of mechanical ventilation. Specific aim 1 will compare the change in oxygenation index during the three-day period in children with acute lung injury by ventilator mode: pressure or volume control. Specific aim 2 will determine the change in pro-inflammatory cytokine concentrations during the three-day period in children with acute lung injury receiving pressure control or volume control ventilation. The proposed research will provide data critical to the understanding of ventilatorinduced lung injury in children with and without chronic lung disease. The results of this study may serve as the basis for a multicenter clinical trial.