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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.