Background: Introducing variability in tidal volume, ventilatory frequency, or both is beneficial during mechanical ventilation in acute respiratory distress syndrome (ARDS). We investigated whether applying cycle-by-cycle variability in the positive end-expiratory pressure (PEEP) exerts beneficial effect on lung function in a model of ARDS.

Methods: Rabbits with lung injury were randomly allocated to receive mechanical ventilation for 6 h by applying a pressure-controlled mode with constant PEEP of 7 cm H₂ O (PC group: n =6) or variable PEEP (VEEP) with a coefficient of variation of 21.4%, range 4-10 cm H₂ O (PC-VEEP group; n =6). Lung oxygenation index (P ao₂ /FiO₂ ) after 6 h of ventilation (H6) was the primary outcome and respiratory mechanics, lung volume, intrapulmonary shunt, and lung inflammatory markers were secondary outcomes.

Results: After lung injury, both groups presented moderate-to-severe ARDS (P ao₂ /FiO₂ <27 kPa). The P ao₂ /FiO₂ was significantly higher in the PC-VEEP group than in the PC group at H6 (12.3 [sd 3.5] vs 19.2 [7.2] kPa, P =0.013) and a lower arterial partial pressure of CO₂ at 1-3 h (P <0.02). The ventilation-induced increases in airway resistance and tissue elastance were prevented by PC-VEEP. There was no evidence for a difference in minute volume, driving pressure, end-tidal CO₂ , lung volumes, intrapulmonary shunt fraction, and cytokines between the ventilation modes.

Conclusions: Prolonged mechanical ventilation with cycle-by-cycle VEEP prevents deterioration in gas exchange and respiratory mechanics in a model of ARDS, suggesting the benefit of this novel ventilation strategy to optimise gas exchange without increasing driving pressure and lung overdistension.