, Volume 29, Issue 8, pp 1345-1353
Date: 16 Apr 2003

Positive end-expiratory pressure modulates local and systemic inflammatory responses in a sepsis-induced lung injury model

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Abstract

Objective

Previous animal studies have shown that certain modes of mechanical ventilation (MV) can injure the lungs. Most of those studies were performed with models that differ from clinical causes of respiratory failure. We examined the effects of positive end-expiratory pressure (PEEP) in the setting of a clinically relevant, in vivo animal model of sepsis-induced acute lung injury ventilated with low or injurious tidal volume.

Methods

Septic male Sprague-Dawley rats were anesthetized and randomized to spontaneous breathing or four different strategies of MV for 3 h at low (6 ml/kg) or high (20 ml/kg) tidal volume (VT) with zero PEEP or PEEP above inflection point in the pressure-volume curve. Sepsis was induced by cecal ligation and perforation. Mortality rates, pathological evaluation, lung tissue cytokine gene expression, and plasma cytokine concentrations were analyzed in all experimental groups.

Results

Lung damage, cytokine synthesis and release, and mortality rates were significantly affected by the method of MV in the presence of sepsis. PEEP above the inflection point significantly attenuated lung damage and decreased mortality during 3 h of ventilation with low VT (25% vs. 0%) and increased lung damage and mortality in the high VT group (19% vs. 50%). PEEP attenuated lung cytokine gene expression and plasma concentrations during mechanical ventilation with low VT.

Conclusions

The use of a PEEP level above the inflection point in a sepsis-induced acute lung injury animal model modulates the pulmonary and systemic inflammatory responses associated with sepsis and decreases mortality during 3 h of MV.

This work was supported by Fondo de Investigación Sanitaria of Spain (#98/1178 and 00/0564)
An editional regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-003-1793-0)