chapter  9
44 Pages

The Role of Cytokines During the Pathogenesis of Ventilator-Associated and Ventilator-Induced Lung Injury

WithJohn A. Belperio, Michael P. Keane, Robert M. Strieter

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS)

are clinical syndromes (hypoxemia, bilateral pulmonary infiltrates, and noncardiogenic pulmonary edema) having multifactorial etiologies either from

direct or indirect injury to the lung (1,2). Histopathologically, there is an

initial acute exudative phase involving an alveolar-capillary leak in conjunc-

tion with leukocyte extravasation. This is followed by a fibroproliferative

phase involving the precipitation of alveolar proteins with hyaline mem-

brane formation, persistent inflammation, and proliferation of alveolar

epithelia and mesenchymal cells. Finally, there is a fibrotic phase in which

inflammation results in dysregulated repair with denudation of the basement membrane, excessive matrix deposition, and parenchymal fibrosis

(1,2). Clinically, these patients develop an increased physiological dead

space, progressive shunt with hypoxemia, decreased compliance, and pul-

monary artery vasculopathy resulting in a high minute ventilation requiring

the need for mechanical ventilation (1). Management has consisted of

aggressive treatment of the inciting cause, vigilant supportive care while

on the ventilator, and the prevention of nosocomial infections. However, the mortality rate from ALI/ARDS is approximately 35% to 65% (1-5). Unfortunately, over the last 30 years there has not been a significant change in

this mortality rate. However, a recent multicentered randomized controlled

trial compared traditional ventilation strategy (tidal volume of 12mL/kg

ideal body weight) to a lung-protective strategy (tidal volume of 6mL/kg

ideal body weight). The study consisted of 861 patients and demonstrated

that the mortality rate in the lung-protective group was 22% lower than in the traditional ventilation group (6). This sentinel study has changed the standard of care for ventilator management of patients with ALI/

ARDS. However, this study has raised questions with regard to possible

mechanism(s) by which the lung-protective strategy reduces mortality.