Science review: mechanisms of ventilator-induced injury

Abstract

Acute respiratory distress syndrome (ARDS) and acute lung injury are among the most frequent reasons for intensive care unit admission, accounting for approximately one-third of admissions. Mortality from ARDS has been estimated as high as 70% in some studies. Until recently, however, no targeted therapy had been found to improve patient outcome, including mortality. With the completion of the National Institutes of Health-sponsored Acute Respiratory Distress Syndrome Network low tidal volume study, clinicians now have convincing evidence that ventilation with tidal volumes lower than those conventionally used in this patient population reduces the relative risk of mortality by 21%. These data confirm the long-held suspicion that the role of mechanical ventilation for acute hypoxemic respiratory failure is more than supportive, in that mechanical ventilation can also actively contribute to lung injury. The mechanisms of the protective effects of low tidal volume ventilation in conjunction with positive end expiratory pressure are incompletely understood and are the focus of ongoing studies. The objective of the present article is to review the potential cellular mechanisms of lung injury attributable to mechanical ventilation in patients with ARDS and acute lung injury.

Figure 1

Potential mechanisms of ventilator-induced lung injury. Mechanical ventilation induces tensile strain and shear forces in the lung. These forces result in increased permeability and disruption of the alveolar–capillary barrier. Mechanical forces also induce an increase in the concentrations of proinflammatory mediators (including IL-1β, tumor necrosis factor alpha, IL-8 and IL-6) in the distal airspaces of the lung. The loss of compartmentalization in the lung results in the release of these mediators into the systemic circulation where they may play a role in end organ dysfunction. Mechanical strain also reduces the active sodium transport-dependent clearance of edema fluid from the airspaces. This potentially contributes to increased edema formation, ongoing lung volume loss, and greater ventilator-associated lung injury.

Figure 2

Static pressure–volume curve of a rat with aspiration-induced acute lung injury. The shaded areas indicate lung volumes where ventilator-associated lung injury is likely to be most severe based on data from experimental studies. Some clinical studies of protective ventilation in acute respiratory distress syndrome patients have used the lower inflection point of the inspiratory limb as a guide to set the positive end expiratory pressure (PEEP). The events associated with this inflection at the alveolar level are uncertain, however, and a clear inflection is not always apparent. The recent National Insitutes of Health-sponsored Acute Respiratory Distress Syndrome Network study that demonstrated a reduction in mortality did not use a pressure–volume curve to set the PEEP [4].

Figure 3

Plasma IL-1β following 4 hours of mechanical ventilation in a rat model of acid aspiration. Ventilation with a tidal volume of 12 ml/kg significantly increased plasma levels of IL-1β compared with rats ventilated with 3 ml/kg and a similar level of positive end expiratory pressure (PEEP; cmH₂O) (*P < 0.05 by paired t test, mean ± standard deviation). IL-1β levels in the 3 ml/kg acid-injured group were not different from those in uninjured rats ventilated with 12 ml/kg or from uninjured, never ventilated rats (n = 5 in each acid injured group and n = 3 in the uninjured groups).