Biotrauma during ultra-low tidal volume ventilation and venoarterial extracorporeal membrane oxygenation in cardiogenic shock: a randomized crossover clinical trial

Laura Amado-Rodríguez, Cecilia Del Busto, Inés López-Alonso, Diego Parra, Juan Mayordomo-Colunga, Miguel Arias-Guillén, Rodrigo Albillos-Almaraz, Paula Martín-Vicente, Cecilia López-Martínez, Covadonga Huidobro, Luigi Camporota, Arthur S Slutsky, Guillermo M Albaiceta, Laura Amado-Rodríguez, Cecilia Del Busto, Inés López-Alonso, Diego Parra, Juan Mayordomo-Colunga, Miguel Arias-Guillén, Rodrigo Albillos-Almaraz, Paula Martín-Vicente, Cecilia López-Martínez, Covadonga Huidobro, Luigi Camporota, Arthur S Slutsky, Guillermo M Albaiceta

Abstract

Background: Cardiogenic pulmonary oedema (CPE) may contribute to ventilator-associated lung injury (VALI) in patients with cardiogenic shock. The appropriate ventilatory strategy remains unclear. We aimed to evaluate the impact of ultra-low tidal volume ventilation with tidal volume of 3 ml/kg predicted body weight (PBW) in patients with CPE and veno-arterial extracorporeal membrane oxygenation (V-A ECMO) on lung inflammation compared to conventional ventilation.

Methods: A single-centre randomized crossover trial was performed in the Cardiac Intensive Care Unit (ICU) at a tertiary university hospital. Seventeen adults requiring V-A ECMO and mechanical ventilation due to cardiogenic shock were included from February 2017 to December 2018. Patients were ventilated for two consecutive periods of 24 h with tidal volumes of 6 and 3 ml/kg of PBW, respectively, applied in random order. Primary outcome was the change in proinflammatory mediators in bronchoalveolar lavage fluid (BALF) between both ventilatory strategies.

Results: Ventilation with 3 ml/kg PBW yielded lower driving pressures and end-expiratory lung volumes. Overall, there were no differences in BALF cytokines. Post hoc analyses revealed that patients with high baseline levels of IL-6 showed statistically significant lower levels of IL-6 and IL-8 during ultra-low tidal volume ventilation. This reduction was significantly proportional to the decrease in driving pressure. In contrast, those with lower IL-6 baseline levels showed a significant increase in these biomarkers.

Conclusions: Ultra-low tidal volume ventilation in patients with CPE and V-A ECMO may attenuate inflammation in selected cases. VALI may be driven by an interaction between the individual proinflammatory profile and the mechanical load overimposed by the ventilator. Trial registration The trial was registered in ClinicalTrials.gov (identifier NCT03041428, Registration date: 2nd February 2017).

Keywords: Extracorporeal membrane oxygenation; Mechanical ventilation; Pulmonary oedema; Respiratory mechanics; Ventilator-induced lung injury.

Conflict of interest statement

ASS is a consultant for Baxter and Xenios. None of the remaining authors have conflicts of interest to disclose.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
CONSORT flow diagram of the study. COPD chronic obstructive pulmonary disease, BAL bronchoalveolar lavage
Fig. 2
Fig. 2
Concentration of IL-6 and IL-8 in bronchoalveolar lavage fluid during ventilation with a tidal volume of 6 ml/kg PBW or 3 ml/kg PBW. Dots and dashed lines show the individual values for each patient. Y-axis is traced using a logarithmic scale. The lower and upper hinges correspond to the first and third quartiles (the 25th and 75th percentiles). The upper and lower whiskers extend from the hinge to the largest or smallest value no further than 1.5 times the interquartile range from the hinge. Individual values are shown as points. Values for a given patient are connected by dashed lines. P values were obtained using a Wilcoxon test for paired data. PBW predicted body weight, IL interleukin
Fig. 3
Fig. 3
Change in IL-6 and IL-8 from ventilation with 6 ml/kg predicted body weight (PBW) to 3 ml/kg PBW in hyperinflamed and non-hyperinflamed patients (defined using a threshold in IL-6 levels during ventilation with 6 ml/kg PBW of 680 pg/ml). The lower and upper hinges correspond to the first and third quartiles (the 25th and 75th percentiles). The upper and lower whiskers extend from the hinge to the largest or smallest value no further than 1.5 times the interquartile range from the hinge. Individual values are shown as points. P values were obtained using an analysis of covariance (ANCOVA) test. IL interleukin
Fig. 4
Fig. 4
Correlation between the change in IL-6 and IL-8 BALF levels from ventilation with 6 ml/kg predicted body weight (PBW) to 3 ml/kg PBW and the corresponding change in driving pressure in hyperinflamed and non-hyperinflamed patients (defined using a threshold in IL-6 levels during ventilation with 6 ml/kg PBW of 680 pg/ml). Note that the x-axis represents the change in driving pressure when tidal volume is decreased, which is mainly defined by compliance of the respiratory system. IL interleukin. P values correspond to the comparison between the two correlation coefficients

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