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

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

doi:10.1016/j.bja.2019.12.040

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

Br J Anaesth. 2020 Apr;124(4):430-439. doi: 10.1016/j.bja.2019.12.040. Epub 2020 Feb 6.

Authors

Jakob Wittenstein¹, Martin Scharffenberg¹, Anja Braune², Robert Huhle¹, Thomas Bluth¹, Moritz Herzog¹, Andreas Güldner¹, Lorenzo Ball³, Francesca Simonassi³, Ines Zeidler-Rentzsch⁴, Marcos F Vidal Melo⁵, Thea Koch¹, Patricia R M Rocco⁶, Paolo Pelosi³, Jörg Kotzerke⁷, Marcelo Gama de Abreu¹, Thomas Kiss⁸

Affiliations

¹ Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
² Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
³ Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy; Anesthesia and Intensive Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, Genoa, Italy.
⁴ Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Department of Orthodontics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁵ Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard University, Boston, MA, USA.
⁶ Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
⁷ Department of Nuclear Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
⁸ Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Electronic address: Thomas.Kiss@ukdd.de.

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.