Effects of variable versus nonvariable controlled mechanical ventilation on pulmonary inflammation in experimental acute respiratory distress syndrome in pigs.

Abstract

Mechanical ventilation with variable tidal volumes (V_T) may improve lung function and reduce ventilator-induced lung injury in experimental acute respiratory distress syndrome (ARDS). However, previous investigations were limited to less than 6 h, and control groups did not follow clinical standards. We hypothesised that 24 h of mechanical ventilation with variable V_T reduces pulmonary inflammation (as reflected by neutrophil infiltration), compared with standard protective, nonvariable ventilation. Experimental ARDS was induced in 14 anaesthetised pigs with saline lung lavage followed by injurious mechanical ventilation. Pigs (n=7 per group) were randomly assigned to using variable V_T or nonvariable V_T modes of mechanical ventilation for 24 h. In both groups, ventilator settings including positive end-expiratory pressure and oxygen inspiratory fraction were adjusted according to the ARDS Network protocol. Pulmonary inflammation (primary endpoint) and perfusion were assessed by positron emission tomography using 2-deoxy-2-[¹⁸F]fluoro-d-glucose and ⁶⁸Gallium (⁶⁸Ga)-labelled microspheres, respectively. Gas exchange, respiratory mechanics, and haemodynamics were quantified. Lung aeration was determined using CT. The specific global uptake rate of ¹⁸F-FDG increased to a similar extent regardless of mode of mechanical ventilation (median uptake for variable V_T=0.016 min^-1 [inter-quartile range, 0.012-0.029] compared with median uptake for nonvariable V_T=0.037 min^-1 [0.008-0.053]; P=0.406). Gas exchange, respiratory mechanics, haemodynamics, and lung aeration and perfusion were similar in both variable and nonvariable V_T ventilatory modes. In a porcine model of ARDS, 24 h of mechanical ventilation with variable V_T did not attenuate pulmonary inflammation compared with standard protective mechanical ventilation with nonvariable V_T.