Abstract
Background: Mechanical ventilation (MV) may initiate or worsen lung injury, so-called ventilator-induced lung injury (VILI). Although different mechanisms of VILI have been identified, research mainly focused on single ventilator parameters. The mechanical power (MP) summarizes the potentially damaging effects of different parameters in one single variable and has been shown to be associated with lung damage. However, to date, the association of MP with pulmonary neutrophilic inflammation, as assessed by positron-emission tomography (PET), has not been prospectively investigated in a model of clinically relevant ventilation settings yet. We hypothesized that the degree of neutrophilic inflammation correlates with MP.Methods: Eight female juvenile pigs were anesthetized and mechanically ventilated. Lung injury was induced by repetitive lung lavages followed by initial PET and computed tomography (CT) scans. Animals were then ventilated according to the acute respiratory distress syndrome (ARDS) network recommendations, using the lowest combinations of positive end-expiratory pressure and inspiratory oxygen fraction that allowed adequate oxygenation. Ventilator settings were checked and adjusted hourly. Physiological measurements were conducted every 6 h. Lung imaging was repeated 24 h after first PET/CT before animals were killed. Pulmonary neutrophilic inflammation was assessed by normalized uptake rate of 2-deoxy-2-[18F]fluoro-D-glucose (KiS), and its difference between the two PET/CT was calculated (ΔKiS). Lung aeration was assessed by lung CT scan. MP was calculated from the recorded pressure–volume curve. Statistics included the Wilcoxon tests and non-parametric Spearman correlation.Results: Normalized 18F-FDG uptake rate increased significantly from first to second PET/CT (p = 0.012). ΔKiS significantly correlated with median MP (ρ = 0.738, p = 0.037) and its elastic and resistive components, but neither with median peak, plateau, end-expiratory, driving, and transpulmonary driving pressures, nor respiratory rate (RR), elastance, or resistance. Lung mass and volume significantly decreased, whereas relative mass of hyper-aerated lung compartment increased after 24 h (p = 0.012, p = 0.036, and p = 0.025, respectively). Resistance and PaCO2 were significantly higher (p = 0.012 and p = 0.017, respectively), whereas RR, end-expiratory pressure, and MP were lower at 18 h compared to start of intervention.Conclusions: In this model of experimental acute lung injury in pigs, pulmonary neutrophilic inflammation evaluated by PET/CT increased after 24 h of MV, and correlated with MP.
Highlights
Mechanical ventilation (MV) is often life-saving in critically ill patients with acute respiratory failure and/or acute respiratory distress syndrome (ARDS) (Bellani et al, 2016)
We aimed to investigate the applied resulting mechanical power (MP) and the neutrophilic pulmonary inflammation in a clinically relevant model of acute lung injury in pigs ventilated with fixed combinations of positive end-expiratory pressure (PEEP) and inspiratory oxygen fractions (FIO2), as recommended by the ARDS network’s low PEEP table (Brower et al, 2004)
The following initial settings were used: Volume-controlled ventilation, tidal volume (VT) 6 ml/kg, PEEP 5 cmH2O, inspiratory to expiratory ratio (I:E) 1:1, inspired fraction of oxygen (FIO2) 1.0, respiratory rate (RR) adjusted to normocapnia, and inspiratory flow 35 L/min (Evita XL, Dräger, Lübeck, Germany)
Summary
Mechanical ventilation (MV) is often life-saving in critically ill patients with acute respiratory failure and/or acute respiratory distress syndrome (ARDS) (Bellani et al, 2016). MV may lead to ventilator-induced lung injury (VILI) (Dreyfuss and Saumon, 1998). Different mechanisms of VILI have been identified so far. Of specific parameters, mechanical energy is inevitably transferred to the respiratory system in every single MV cycle, resulting in transferred mechanical power (MP) when multiplied with respiratory rate (RR). Different mechanisms of VILI have been identified, research mainly focused on single ventilator parameters. The mechanical power (MP) summarizes the potentially damaging effects of different parameters in one single variable and has been shown to be associated with lung damage. To date, the association of MP with pulmonary neutrophilic inflammation, as assessed by positron-emission tomography (PET), has not been prospectively investigated in a model of clinically relevant ventilation settings yet. We hypothesized that the degree of neutrophilic inflammation correlates with MP
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