Acute Lung Injury

It has been recognized for some time that mechanical ventilation may induce lung injury. High tidal volume (Vt) ventilation is detrimental and has been shown to result in increased mortality.

Vt ventilation is regarded as a lung protective strategy. Acute lung injury (ALI) is characterized by decreased pulmonary compliance, alveolar flooding, and inhomogeneous ventilation in the presence of atelectatic lung. The size of the remaining open lung is unknown, and a Vt adjusted to body weight (BW) may not be appropriate. Consequently, overdistension of ventilated units may still occur although a small Vt is administered. A practical parameter of increased mechanical stress of the lung remains to be demonstrated.

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Experiments have demonstrated that pulmonary nitric oxide production is stimulated by mechanical forces. High-frequency oscillatory ventilation for example leads to an increase in exhaled nitric oxide in rabbits. Preliminary data from our laboratory suggest that nitrite (NO2~) concentration in BAL fluid (BALF) of rabbit lungs are influenced strongly by Vt. We therefore investigated the applicability of this parameter that is also easy to determine. Increased production of nitric oxide has often been related to inflammatory processes, such as asthma and cystic fibrosis. Mechanical ventilation may also contribute to lung injury and inflammation. Pulmonary nitric oxide release in patients receiving mechanical ventilation may therefore reflect alveolar distension, inflammation, or both. Our study addresses the question whether pulmonary nitric oxide production is related predominately to mechanical factors or to inflammation (pulmonary or systemic).

BALF has been used for monitoring of various pulmonary disorders including ARDS. The procedure is not without complications in the critically ill, and is not suited for multiple repetition. In addition, the dilution factor of epithelial lung fluid (ELF) in BALF varies to some extent, making measurements of solutes and other constituents difficult. Exhaled breath condensate (EBC) is a novel, noninvasive technique of sampling the lining fluid of the lung. EBC has been used for monitoring inflammatory lung diseases such as asthma, COPD, interstitial lung disease, and the ARDS. Hydrogen peroxide, isoprostanes, eicosanoids, cytokines, and also nitrite have all been detected in EBC.