chapter  16
28 Pages

Genomic Insights into Ventilator-Induced Lung Injury

WithStephanie A. Nonas, Jeffrey R. Jacobson, Joe G. N. Garcia

The institution of mechanical ventilation remains a life-saving intervention

in patients with acute lung injury (ALI), a devastating clinical syndrome defined by acute respiratory failure with lung inflammation, increased vas-

cular permeability, and alveolar edema. ALI represents a final common

pathway of response to a variety of insults (sepsis, trauma, pneumonia,

etc.) and despite recent advances, still carries an annual mortality rate

of 30% to 50% (1). Mechanical ventilation, although a necessary part of

therapy, is known to worsen existing ALI and may even be a primary

cause of ALI (2,3). During mechanical ventilation, a high end-inspiratory

lung volume [from large tidal volumes (VTs) or high levels of positive end-expiratory pressure (PEEP)] results in high-permeability pulmonary

edema known as ventilator-associated lung injury (VALI). High volume

mechanical ventilation is now recognized to be potentially directly harmful

to susceptible patients, with the benefit of reducing airway pressures by

ventilating with lower VTs in ALI patients [and its most severe form-acute respiratory distress syndrome (ARDS)] firmly established by the landmark

ARDSNet findings, which demonstrated a significant decrease in mortality from ARDS with a reduction in VT from 12 to 6mL/kg (4). In addition to directly inducing lung injury, each day on the ventilator prolongs sedation

requirements and increases the risk of developing malnutrition and nosoco-

mial-and ventilator-associated pneumonia. These findings have spurred the

research on VALI.