Lung Metabolism During Ventilator-Induced Lung Injury

Abstract

Concerns about pulmonary complications of positive pressure ventilation (1) are at least as old as the description of the Acute Respiratory Distress Syndrome (ARDS) (2). Yet, it took about a decade until experimental findings (3) shifted the focus from air leaks and oxygen toxicity to the biological effects of large excursions of the lung parenchyma (4). The demonstration that mechanical ventilation with high peak inspiratory pressures and low positive end-expiratory pressure (PEEP) could produce edema, increased alveolo-capillary permeability, leukocyte infiltration, and inflammation in normal lungs established the current understanding of ventilator-induced lung injury (VILI) (4, 5). The clinical relevance of VILI was confirmed by the demonstration of a 22% decrease in mortality of ARDS patients when lung stretch was reduced through lower tidal volumes (VT). (6). In addition to excessive lung stretch due to large VT, it has been recognized that VILI can also be caused by low end-expiratory lung volumes, even at low airway pressures. Mechanisms proposed to explain such injury include concentration of stresses in the heterogeneously expanding lung parenchyma (7), and propagation and rupture of liquid plugs producing injurious fluid mechanical stresses during cyclic recruitment-derecruitment of distal lung units (8, 9). Mitigation of these low-volume phenomena by optimizing lung recruitment with higher PEEP levels (10) and proning (11) has been beneficial in patients with moderate and severe ARDS. However, despite the large number of experimental and clinical studies, uncertainty persists about the relative contribution of overdistension versus low-volume injury to the ultimate lung damage produced by VILI (12). Topographically, in supine patients, nondependent (ventral) injury would be expected if overdistension would predominate (13), whereas dependent (dorsal) damage would be expected for predominant low-volume injury (14). The clinical relevance of the topic has been emphasized by the suggestion that the mass of opening-closing lung is an independent risk factor for death in patients with ARDS (15), and that regional forces during mechanical ventilation determine lung parenchyma abnormalities found in ARDS survivors (16).