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

Wittenstein, Jakob; Scharffenberg, Martin; Braune, Anja; Huhle, Robert; Bluth, Thomas; Herzog, Moritz; Güldner, Andreas; Ball, Lorenzo; Simonassi, Francesca; Zeidler-Rentzsch, Ines; Vidal Melo, Marcos F.; Koch, Thea; Rocco, Patricia R.M.; Pelosi, Paolo; Kotzerke, Jörg; Gama de Abreu, Marcelo; Kiss, Thomas

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-[(18)F]fluoro-d-glucose and (68)Gallium ((68)Ga)-labelled microspheres, respectively. Gas exchange, respiratory mechanics, and haemodynamics were quantified. Lung aeration was determined using CT. RESULTS: The specific global uptake rate of (18)F-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).