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Increasing the inspiratory time and I:E ratio during mechanical ventilation aggravates ventilator-induced lung injury in mice

Holger Müller-Redetzky, Matthias Felten, Marfa Polikarpova, Katharina Hellwig, Sandra Wienhold, Jan Naujoks, Bastian Opitz, Olivia Kershaw, Achim Gruber, Norbert Suttorp, Martin Witzenrath
European Respiratory Journal 2014 44: 1387; DOI:
Holger Müller-Redetzky
1Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Matthias Felten
1Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Marfa Polikarpova
1Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Katharina Hellwig
1Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Sandra Wienhold
1Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Jan Naujoks
1Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Bastian Opitz
1Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Olivia Kershaw
2Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany
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Achim Gruber
2Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany
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Norbert Suttorp
1Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Martin Witzenrath
1Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Abstract

Rationale: Increasing the inspiratory time and thereby the inspiratory/expiratory ratio (I:E ratio) during mechanical ventilation may improve oxygenation but may also be harmful as the absolute stress over time increases. We thus hypothesized that increasing inspiratory time and I:E ratio aggravates VILI.

Methods: VILI was induced in mice by high tidal volume ventilation (HVT 34 ml/kg). Low tidal volume ventilation (LVT 8 ml/kg) was used in control groups. HVT and LVT mice were ventilated with either I:E of 1:2 (LVT 1:2, HVT 1:2) or 1:1 (LVT 1:1, HVT 1:1) for 4h or until an alternative endpoint (mean arterial blood pressure below 40 mmHg). Survival, lung compliance, oxygenation, pulmonary permeability, pulmonary and systemic inflammation (leukocyte differentiation, qPCR and ELISA of pulmonary IL-6, IL-1b, KC, CCL2) was analysed.

Results: LVT 1:2 or LVT 1:1 did not result in VILI, all individuals survived the ventilation period. HVT 1:2 induced a decrease of pulmonary compliance, increased pulmonary neutrophils and cytokines. All animals survived. HVT 1:1 caused a further significant worsening of oxygenation, compliance, pulmonary proinflammatory cytokine expression, BALF and blood neutrophils. In the HVT 1:1 group, significant mortality during MV was observed.

Conclusion: According to the "baby lung" concept, mechanical ventilation associated stress in overinflated regions of ARDS lungs was simulated using high tidal volume ventilation. Increase of inspiratory time and I:E ratio significantly augmented VILI in mice. Thus, increasing the inspiratory time and I:E ratio in ARDS patients during MV should be critically reconsidered.

  • Lung injury
  • ARDS (Acute Respiratory Distress Syndrome)
  • Mechanical ventilation - interactions and complications
  • © 2014 ERS
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Increasing the inspiratory time and I:E ratio during mechanical ventilation aggravates ventilator-induced lung injury in mice
Holger Müller-Redetzky, Matthias Felten, Marfa Polikarpova, Katharina Hellwig, Sandra Wienhold, Jan Naujoks, Bastian Opitz, Olivia Kershaw, Achim Gruber, Norbert Suttorp, Martin Witzenrath
European Respiratory Journal Sep 2014, 44 (Suppl 58) 1387;

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Increasing the inspiratory time and I:E ratio during mechanical ventilation aggravates ventilator-induced lung injury in mice
Holger Müller-Redetzky, Matthias Felten, Marfa Polikarpova, Katharina Hellwig, Sandra Wienhold, Jan Naujoks, Bastian Opitz, Olivia Kershaw, Achim Gruber, Norbert Suttorp, Martin Witzenrath
European Respiratory Journal Sep 2014, 44 (Suppl 58) 1387;
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