ABSTRACT
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.
