Effect of patient-ventilator asynchrony on lung and diaphragmatic injury in experimental acute respiratory distress syndrome in a porcine model

Jakob Wittenstein; Robert Huhle; Mark Leiderman; Marius Möbius; Anja Braune; Sebastian Tauer; Paul Herzog; Giulio Barana; Alessandra de Ferrari; Andrea Corona; Thomas Bluth; Thomas Kiss; Andreas Güldner; Marcus J Schultz; Patricia R M Rocco; Paolo Pelosi; Marcelo Gama de Abreu; Martin Scharffenberg

doi:10.1016/j.bja.2021.10.037

Effect of patient-ventilator asynchrony on lung and diaphragmatic injury in experimental acute respiratory distress syndrome in a porcine model

Br J Anaesth. 2023 Jan;130(1):e169-e178. doi: 10.1016/j.bja.2021.10.037. Epub 2021 Nov 10.

Authors

Jakob Wittenstein¹, Robert Huhle¹, Mark Leiderman¹, Marius Möbius², Anja Braune³, Sebastian Tauer¹, Paul Herzog¹, Giulio Barana⁴, Alessandra de Ferrari⁵, Andrea Corona⁶, Thomas Bluth¹, Thomas Kiss⁷, Andreas Güldner¹, Marcus J Schultz⁸, Patricia R M Rocco⁹, Paolo Pelosi¹⁰, Marcelo Gama de Abreu¹¹, Martin Scharffenberg¹

Affiliations

¹ Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.
² Neonatology and Pediatric Critical Care Medicine, Department of Pediatrics, University Hospital and Medical Faculty Carl Gustav Carus, Dresden, Germany.
³ Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden, Dresden, Germany; Department of Nuclear Medicine, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
⁴ Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden, Dresden, Germany; Department of Anaesthesiology, Hospital Thurgau AG, Frauenfeld, Switzerland.
⁵ Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden, Dresden, Germany; Department of Anaesthesia and Intensive Care, IRCCS AOU San Martino IST, Genoa, Italy.
⁶ Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden, Dresden, Germany; Department of Anaesthesiology and Intensive Care, Mater Olbia Hospital, Olbia, Italy.
⁷ Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden, Dresden, Germany; Department of Anaesthesiology, Intensive-, Pain- and Palliative Care Medicine, Radebeul Hospital, Academic Hospital of the Technische Universität Dresden, Radebeul, Germany.
⁸ Department of Intensive Care and Laboratory of Experimental Intensive Care and Anaesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
⁹ Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
¹⁰ Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy.
¹¹ Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden, Dresden, Germany; Department of Intensive Care and Resuscitation, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: gamadem@ccf.org.

PMID: 34895719
DOI: 10.1016/j.bja.2021.10.037

Abstract

Background: Patient-ventilator asynchrony during mechanical ventilation may exacerbate lung and diaphragm injury in spontaneously breathing subjects. We investigated whether subject-ventilator asynchrony increases lung or diaphragmatic injury in a porcine model of acute respiratory distress syndrome (ARDS).

Methods: ARDS was induced in adult female pigs by lung lavage and injurious ventilation before mechanical ventilation by pressure assist-control for 12 h. Mechanically ventilated pigs were randomised to breathe spontaneously with or without induced subject-ventilator asynchrony or neuromuscular block (n=7 per group). Subject-ventilator asynchrony was produced by ineffective, auto-, or double-triggering of spontaneous breaths. The primary outcome was mean alveolar septal thickness (where thickening of the alveolar wall indicates worse lung injury). Secondary outcomes included distribution of ventilation (electrical impedance tomography), lung morphometric analysis, inflammatory biomarkers (gene expression), lung wet-to-dry weight ratio, and diaphragmatic muscle fibre thickness.

Results: Subject-ventilator asynchrony (median [interquartile range] 28.8% [10.4] asynchronous breaths of total breaths; n=7) did not increase mean alveolar septal thickness compared with synchronous spontaneous breathing (asynchronous breaths 1.0% [1.6] of total breaths; n=7). There was no difference in mean alveolar septal thickness throughout upper and lower lung lobes between pigs randomised to subject-ventilator asynchrony vs synchronous spontaneous breathing (87.3-92.2 μm after subject-ventilator asynchrony, compared with 84.1-95.0 μm in synchronised spontaneous breathing;). There were also no differences between groups in wet-to-dry weight ratio, diaphragmatic muscle fibre thickness, atelectasis, lung aeration, or mRNA expression levels for inflammatory cytokines pivotal in ARDS pathogenesis.

Conclusions: Subject-ventilator asynchrony during spontaneous breathing did not exacerbate lung injury and dysfunction in experimental porcine ARDS.

Keywords: acute respiratory distress syndrome; diaphragm injury; lung injury; lung morphometry; mechanical ventilation; spontaneous breathing; subject–ventilator asynchrony.

MeSH terms

Animals
Female
Lung Injury*
Pulmonary Alveoli
Respiration, Artificial / adverse effects
Respiratory Distress Syndrome* / therapy
Swine
Thoracic Injuries*
Ventilators, Mechanical