Clinical review: Early treatment of acute lung injury--paradigm shift toward prevention and treatment prior to respiratory failure

Abstract

Acute lung injury (ALI) remains a major cause of morbidity and mortality in critically ill patients. Despite improved understanding of the pathogenesis of ALI, supportive care with a lung protective strategy of mechanical ventilation remains the only treatment with a proven survival advantage. Most clinical trials in ALI have targeted mechanically ventilated patients. Past trials of pharmacologic agents may have failed to demonstrate efficacy in part due to the resultant delay in initiation of therapy until several days after the onset of lung injury. Improved early identification of at-risk patients provides new opportunities for risk factor modification to prevent the development of ALI and novel patient groups to target for early treatment of ALI before progression to the need for mechanical ventilation. This review will discuss current strategies that target prevention of ALI and some of the most promising pharmacologic agents for early treatment of ALI prior to the onset of respiratory failure that requires mechanical ventilation.

Figure 1

Proportion of patients who developed acute lung injury (ALI) according to tidal volume in patients mechanically ventilated for >48 hours without ALI at time of intubation. Tidal volume (Vt) ≤ 9 ml/kg predicted body weight (PBW; n = 66); Vt 9 to 12 ml/kg PBW (n = 160); Vt ≥ 12 ml/kg PBW (n = 100). *Adjusted P-value from a multiple logistic regression model including tidal volume, transfusion, postoperative, height, female gender, restrictive lung disease, and acidosis (pH <7.35); tidal volume was treated as a continuous variable. Reprinted from [34] with permission from Critical Care Medicine.

Figure 2

Kaplan-Meier curve of incidence of acute lung injury (left), percentage of patients weaned from ventilator (middle), and mortality (right) in patients mechanically ventilated with conventional tidal volume (solid circles) or lower tidal volumes (open circles). ALI, acute lung injury; ARDS, acute respiratory distress syndrome. Reprinted from [35] with permission from Critical Care.

Figure 3

Trends in age- and sex-specific incidence of acute respiratory distress syndrome from 2001 to 2008 in Olmsted County, Minnesota (incidence obtained by validated screening of ICU admission within Mayo Clinic). Dotted lines represent 95% confidence intervals. ALI, acute lung injury. Reprinted from [41] with permission of the American Thoracic Society. Copyright © 2012 American Thoracic Society. Official Journal of the American Thoracic Society.

Figure 4

Effects of simvastatin on pulmonary and nonpulmonary organ function. Patients with acute lung injury/acute respiratory distress syndrome were treated with 80 mg simvastatin (gray bars) or placebo (white bars). (a) Simvastatin reduces oxygenation index (OI) at day 14 but does not reach statistical significance. Data are mean and standard deviation. (b) Simvastatin reduces plateau pressure at day 14 but does not reach statistical significance. Data are mean and standard deviation. (c) Simvastatin reduces lung injury score (LIS) at day 14 but does not reach statistical significance. Data are mean and standard deviation. (d) Simvastatin reduces Sequential Organ Failure Assessment (SOFA) score at day 14. Data are median (interquartile range). * P < 0.05 versus placebo. Reprinted from [64] with permission of the American Thoracic Society. Copyright © 2012 American Thoracic Society. Official Journal of the American Thoracic Society.