Background: Breath stacking, particularly double triggering, is a common patient-ventilator asynchrony during strong inspiratory effort. It can cause excessive tidal volumes and high transpulmonary pressures, contributing to ventilator-induced lung injury (VILI). The mode-specific consequences of breath stacking induced by strong inspiratory effort remain unclear.

Methods: In a porcine model of minimal lung injury, 17 animals were randomized to volume-controlled ventilation (VCV, n = 9) or pressure-controlled ventilation (PCV, n = 8). High respiratory drive was induced with continuous CO₂ inhalation, and ventilator settings were dynamically adjusted to maintain a breath stacking ratio of 40-70% of spontaneous efforts. Measurements included airway and transpulmonary pressures, driving pressures, tidal volume, esophageal pressure swings (ΔPes), stress index (SI), respiratory compliance, and histological lung injury. Risk factors for baro/volutrauma were defined by elevated plateau or driving pressures, transpulmonary pressures, or tidal volume >10 mL/kg. Atelectrauma risk was defined by SI < 0.9, negative end-expiratory transpulmonary pressure (PLexp), or vigorous effort (ΔPes > 5 cmH₂O or Pmus > 8 cmH₂O).

Results: VCV animals exhibited higher respiratory rates (44.0 vs. 30.5 breaths/min, p = 0.027), whereas PCV resulted in stronger inspiratory efforts (ΔPes 6.1 vs. 4.2 cmH₂O, p = 0.015). During breath stacking, VCV produced larger tidal volumes and higher plateau pressures, accumulating more baro/volutrauma risk factors (median 4.0 vs. 0.0, p < 0.001). In contrast, PCV animals developed more atelectrauma risk factors (3.0 vs. 1.0, p = 0.004). Histological injury scores were comparable, with a non-significant trend toward greater severity in PCV.

Conclusions: Breath stacking under strong inspiratory drive can promote lung injury through distinct mechanisms depending on ventilation mode. VCV was associated with the risk of overdistension, whereas PCV involved vigorous inspiratory effort and potential atelectrauma. Double triggering should be recognized as a clinical warning sign, prompting careful assessment of respiratory drive, inspiratory effort, and ventilator settings.