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

Abstract

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.

Keywords: ARDS; mechanical ventilation; positron emission tomography; pulmonary neutrophilic inflammation; variable ventilation.

Fig 1

Transversal slices of inflammation, aeration, and perfusion of one representative animal per group before and 24 h after randomisation. Left column: transversal slice of the specific uptake rates of 2-deoxy-2-[¹⁸F]fluoro-d-glucose (K_iS). K_iS was determined with positron emission tomography/CT and kinetic modelling according to the Patlak method. The resulting K_i values were normalised to the tissue fraction (K_iS=K_i/F_TISSUE=K_i/(1 – gas fraction – blood fraction); gas fraction determined from CT; blood fraction determined using the Sokoloff three-compartment model). Middle column: aeration compartments obtained from CT; hyper, hyper-aerated compartment; normally, normally aerated compartment; poorly, poorly aerated compartment; non, nonaerated compartment. Right column: distribution of perfusion obtained with ⁶⁸Ga-labelled microspheres and positron emission tomography/CT. VV, variable ventilation; NV, nonvariable ventilation; Day 1, before randomisation; Day 2, 24 h after randomisation.

Fig 2

Regional specific uptake rates of 2-deoxy-2-[¹⁸F]fluoro-d-glucose (K_iS) before and 24 h after randomisation. K_iS were determined by positron emission tomography/CT and kinetic modelling according to the Patlak method. Resulting K_i values were normalised to tissue fraction (K_iS=K_i/F_TISSUE=K_i/(1–gas fraction–blood fraction); gas fraction was determined from CT; blood fraction determined using the Sokoloff three-compartment model). Symbols and horizontal lines represent the median and inter-quartile range. Global statistical significance was accepted at P<0.05, Bonferroni–Holm adjustment for multiple testing. Differences between Day 1 and Day 2 within the same region and group were tested with Wilcoxon test (depicted P-values). No differences were found between groups VV and NV (Mann–Whitney U-test). n=7 per group. VV, variable ventilation; NV, nonvariable ventilation. Day 1, before randomisation; Day 2, 24 h after randomisation.

Fig 3

Size of aeration compartments of the whole lung expressed as % mass of the whole lung. Bars represent the mean values of the hyper aerated (blue), normally aerated (green), poorly aerated (yellow), and nonaerated compartments (red). Vertical lines represent standard deviations. Global statistical significance was accepted at P<0.05, Bonferroni–Holm adjustment for multiple testing. Differences between Day 1 and Day 2 within the same group and same compartment were tested with Wilcoxon tests (depicted P-values). No differences were found between groups VV and NV (Mann–Whitney U-test). n=7 per group. VV, variable ventilation; NV, nonvariable ventilation; Day 1, before randomisation; Day 2, 24 h after randomisation.

Fig 4

Specific regional pulmonary perfusion in regions of equal lung mass from ventral to dorsal determined by positron emission tomography/CT and ⁶⁸Ga-labelled microspheres. Symbols and horizontal lines represent median and inter-quartile ranges. Global statistical significance was accepted at P<0.05, Bonferroni–Holm adjustment for multiple testing. Differences between Day 1 and Day 2 within the same group and same region were tested with Wilcoxon tests (depicted P-values). No differences were found between groups VV and NV (Mann–Whitney U-test). n=7 per group. VV, variable ventilation; NV, nonvariable ventilation; Day 1, before randomisation; Day 2, 24 h after randomisation.