Resolution of pulmonary edema with variable mechanical ventilation in a porcine model of acute lung injury

Abstract

Objective Resolution of the acute respiratory distress syndrome (ARDS) requires clearance of pulmonary edema. Biologically variable ventilation (BVV) strategies that improve gas exchange, lung mechanics, and inflammatory mediators in ARDS may be beneficial in this regard. We used quantitative computed tomography (CT), a single indicator thermodilution system (PiCCOÒ) to determine extravascular lung water (EVLW), and the change in edema protein concentration over time to compare edema clearance with BVV vs conventional mechanical ventilation (CMV) in a porcine ARDS model. Methods Sixteen pigs with oleic acid lung injury were randomized to four hours of ventilation with either CMV (n = 8) or BVV (n = 8) at identical low tidal volume and minute ventilation over time. Hemodynamic variables, gas exchange, lung mechanics, and PiCCO derived EVLW were determined hourly. Computed tomography images and edema fluid samples were obtained at baseline lung injury and after four hours of ventilation. Wet and dry lung weights were determined postmortem.Results At four hours with BVV, peak airway pressure was decreased significantly and lung compliance improved compared with CMV (P = 0.003; P \ 0.001, respectively). Hemodynamic variables and gas exchange were not different between groups. Also at four hours, computed tomography revealed an increase in total gas volume (P = 0.001) and a decrease in total lung weight and global lung density (P = 0.005; P = 0.04 respectively) with BVV. These findings were associated with a significant increase in the gas volume of normally aerated lung regions (P \ 0.001) and a decrease in the poorly and non-aerated lung regions (P = 0.001). No change in any CT parameter occurred with CMV. The lung weights derived from computed tomography correlated well with postmortem wet weights (R 2 = 0.79; P \ 0.01). The decrease in PiCCO derived EVLW from injury to four hours did not differ significantly between BVV and CMV. Extravascular lung water showed no correlation with postmortem wet weights and significantly underestimated lung water. Average alveolar fluid clearance rates were positive (1.4%Áhr -1 (3%)) with BVV and negative with CMV (-2.0%Áhr -1 (4%)). Conclusions In a comparison between BVV and CMV, computed tomography evidence suggests that BVV facilitates enhanced clearance and/or redistribution of edema fluid with improved recruitment of atelectatic and poorly aerated lung regions; no such evidence was seen with either single thermodilution measurement of EVLW or edema clearance rates. The results of computed tomography provide further evidence of the benefit of BVV over conventional ventilation in ARDS. RésuméObjectif La re´solution d'un syndrome de de´tresse respiratoire aigue¨(SDRA) ne´cessite l'e´limination de

Variable Ventilation from Bench to Bedside

“…In a porcine oleic acid model, total lung weight and density were reduced with variable controlled mechanical ventilation compared to conventional controlled mechanical ventilation and average alveolar fluid clearance rates were positive compared to negative [34]. However, analysis of corresponding wet:dry ratios of the post-mortem lung showed no effects of variable controlled mechanical ventilation compared to conventional controlled mechanical ventilation in five out of six investigations, independent of the injury model [13, 29-31, 34, 44].…”

“…Similarly, venous admixture was reduced in variable PSV but not in conventional PSV [16,36]. In a model of lung injury induced by oleic acid in pigs [13,14,34], variable controlled mechanical ventilation did not importantly influence the dead space, suggesting that shunt reduction is more prominent then reduction of dead space during variable ventilation.…”

“…In 10 out of 12 experimental studies [13][14][15][27][28][29][30][31][32][33][34][35] in different species and models of ARDS, respiratory system compliance (C RS ) was positively influenced by variable [18]. ΔP supp : change in support pressure needed to gain the displayed tidal volume (V T ) in variable ventilation controlled mechanical ventilation.…”

Variability in Mechanical Ventilation: What's All the Noise About?

“…Furthermore, variable ventilation also facilitates more uniform lung recruitment during acute lung injury. Using computed tomography in a porcine oleic acid-induced lung injury model, Graham et al 28,29 demonstrated significantly improved recruitment of nonaerated and poorly aerated lung areas without a concomitant increase in hyperaerated lung areas. In addition, there is evidence that the recruitment associated with variable ventilation is more sustained than that with monotonous controlled mechanical ventilation when used in conjunction with PEEP.…”

Fractals in Clinical Hemodynamics

“…[7][8][9] Novel ventilator modes, such as adaptive servo ventilation, demonstrate that application of variable support in one physiologic system (respiratory system) promotes variable physiology in a linked system (cardiac). 10 What can we conclude from the article by Bishop et al, which shows us that a vasoconstrictor alters the fractal dimension of the blood pressure (but not the heart rate) while atropine alters the fractal dimension of the heart rate (but not the blood pressure)?…”