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Crit Care. 2015 Jan 28;19:23. doi: 10.1186/s13054-015-0759-2.

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

Author information

1
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. holger.mueller-redetzky@charite.de.
2
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. matthias.felten@charite.de.
3
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. katharina.hellwig@charite.de.
4
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. sandra.wienhold@charite.de.
5
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. jan.naujoks@charite.de.
6
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. bastian.opitz@charite.de.
7
Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany. olivia.kershaw@fu-berlin.de.
8
Department of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany. achim.gruber@fu-berlin.de.
9
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. norbert.suttorp@charite.de.
10
Department of Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. martin.witzenrath@charite.de.

Abstract

INTRODUCTION:

Lung-protective ventilation reduced acute respiratory distress syndrome (ARDS) mortality. To minimize ventilator-induced lung injury (VILI), tidal volume is limited, high plateau pressures are avoided, and positive end-expiratory pressure (PEEP) is applied. However, the impact of specific ventilatory patterns on VILI is not well defined. Increasing inspiratory time and thereby the inspiratory/expiratory ratio (I:E ratio) may improve oxygenation, but may also be harmful as the absolute stress and strain over time increase. 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 9 ml/kg) was used in control groups. PEEP was set to 2 cm H2O, FiO2 was 0.5 in all 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 4 hours or until an alternative end point, defined as mean arterial blood pressure below 40 mm Hg. Dynamic hyperinflation due to the increased I:E ratio was excluded in a separate group of animals. Survival, lung compliance, oxygenation, pulmonary permeability, markers of pulmonary and systemic inflammation (leukocyte differentiation in lung and blood, analyses of pulmonary interleukin-6, interleukin-1β, keratinocyte-derived chemokine, monocyte chemoattractant protein-1), and histopathologic pulmonary changes were analyzed.

RESULTS:

LVT 1:2 or LVT 1:1 did not result in VILI, and all individuals survived the ventilation period. HVT 1:2 decreased lung compliance, increased pulmonary neutrophils and cytokine expression, and evoked marked histologic signs of lung injury. All animals survived. HVT 1:1 caused further significant worsening of oxygenation, compliance and increased pulmonary proinflammatory cytokine expression, and pulmonary and blood neutrophils. In the HVT 1:1 group, significant mortality during mechanical ventilation was observed.

CONCLUSION:

According to the "baby lung" concept, mechanical ventilation-associated stress and strain in overinflated regions of ARDS lungs was simulated by using high tidal-volume ventilation. Increase of inspiratory time and I:E ratio significantly aggravated VILI in mice, suggesting an impact of a "stress/strain × time product" for the pathogenesis of VILI. Thus increasing the inspiratory time and I:E ratio should be critically considered.

PMID:
25888164
PMCID:
PMC4336519
DOI:
10.1186/s13054-015-0759-2
[Indexed for MEDLINE]
Free PMC Article

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