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

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.