Modeling the time-course of ventilator-induced lung injury: what can we learn from interspecies discrepancies?

Abstract

Alterations in lung fluid balance, increases in endothelial and epithelial permeability, and severe tissue damage have been widely described in animals following injurious mechanical ventilation and regrouped under the term ventilator-induced lung injury (VILI) [1]. The clinical relevance of VILI was highlighted by the acute respiratory distress syndrome (ARDS) Network trial that showed a 22% reduction of mortality in patients with ARDS when the mechanical stress applied to the lungs was lessened by reducing the tidal volume applied [2]. The pathophysiology of VILI is unequivocal, and several mechanical determinants of VILI have been identified to date: (1) regional overdistension caused by the application of a local stress or pressure that forces cells and tissues to assume shapes and dimensions that they do not assume during unassisted breathing [3][4][5]; (2) so-called ''low volume injury'' associated with the cyclic recruitment-derecruitment of lung units [6], which causes abrasion of the epithelial airspace lining by interfacial forces [7]; (3) inactivation of surfactant triggered by large alveolar surface area oscillations [8]; (4) the interdependence mechanism that raises cell and tissue stress between neighboring structures with differing mechanical properties [9]. Early experimental studies demonstrated that the main determinant of VILI is lung end-inspiratory volume, associated with high transpulmonary pressures [10,11]. Thus, the term ''volutrauma'' is preferred to the term ''barotrauma'', since the absolute level of airway pressure per se is not injurious [10].The severity of VILI depends both on the degree (as determined by ventilator settings) and duration of the mechanical insult applied to the lungs and on the sensitivity of the lungs to VILI, which differs according to animal species. For example, Webb and Tierney demonstrated that rats subjected to mechanical ventilation using peak inspiratory pressures of 30 or 45 cmH 2 O developed pulmonary edema within 60 and 20 min, respectively, following its onset [3], and Dreyfuss et al. showed that pulmonary edema occurred after only 5 min of injurious mechanical ventilation in healthy rats [5]. In contrast, in larger animal species, longer ventilation periods and higher peak inspiratory pressures are required for the development of VILI: lambs mechanically ventilated at 58 cmH 2 O peak inspiratory pressures for 6 h only developed mild pulmonary edema [12], and the average time required for the development of impairment in gas exchanges and pulmonary mechanics in sheep ventilated with 50 cmH 2 O peak inspiratory pressures was 24 h [13].

Influence of Inspiration to Expiration Ratio on Cyclic Recruitment and Derecruitment of Atelectasis in a Saline Lavage Model of Acute Respiratory Distress Syndrome*

“…A s a life-saving therapy, the majority of patients with acute respiratory distress syndrome (ARDS) require mechanical ventilation to support the failing lungs, but this in turn raises the risk of ventilator-induced lung injury (VILI) (1). Reducing tidal volume (Vt) improves both mortality and morbidity (2-4).…”

Year in review in Intensive Care Medicine 2011: III. ARDS and ECMO, weaning, mechanical ventilation, noninvasive ventilation, pediatrics and miscellanea

“…It was concluded that lung strain may play a critical role as a unifying rule describing the development of VILI among mammals with healthy lungs. This article is accompanied by an editorial comment by de Prost et al [29]. …”