Computationally-directed mechanical ventilation in a porcine model of ARDS

Background Despite the implementation of protective mechanical ventilation, ventilator-induced lung injury remains a significant driver of ARDS-associated morbidity and mortality. Mechanical ventilation must be personalized and adaptive for the patient and evolving disease course to achieve sustained improvements in patient outcomes. In this study, we modified a military-grade transport ventilator to deliver the airway pressure release ventilation (APRV) modality. We developed a computationally-directed (CD) method of adjusting the expiratory duration (T Low ) during APRV using physiologic feedback to reduce alveolar derecruitment and tested this modality in a porcine model of moderate-to-severe ARDS. Methods Female Yorkshire-cross pigs (n = 27) were ventilated using a ZOLL EMV+® 731 Series ventilator during general anesthesia and subjected to a heterogeneous Tween lung injury followed by injurious mechanical ventilation. Animals were subsequently ventilated for 6 hours under general anesthesia after randomization to one of three groups: V T 6 (n = 9) with a tidal volume (V T ) of 6 mL/kg and stepwise adjustments in PEEP and FiO 2 ; V T 10 (n = 9) with V T of 10 mL/kg and PEEP of 5 cmH 2 O; CD-APRV group (n = 9) with computationally-directed adjustments in T Low based on a nonlinear equation of motion to describe respiratory mechanics. Results are reported as median interquartile range. Results All groups developed moderate-to-severe ARDS and had similar recovery in lung injury, with all demonstrating final PaO 2 :FiO 2 300 mmHg (V T 6: 415.5 383.0–443.4, V T 10: 353.3 297.3–397.7, CD-APRV: 316.6 269.8–362.4; p = 0.12). PaCO 2 was significantly higher in the V T 6 group compared with the CD-APRV group (59.3 52.3–60.1 mmHg vs. 38.5 32.7–52.2 mmHg, p = 0.04) but not significantly different from the V T 10 group (47.5 45.3–54.4 mmHg; p = 0.32 vs. V T 6) despite having a significantly higher respiratory rate (30.0 30.0–32.0 breaths/min) compared with V T 10 (12.0 12.0–15.0 breaths/min, p = 0.001) and CD-APRV (14.0 14.0–14.0 breaths/min, p 0.001) groups at the study end. Conclusion We successfully implemented a computationally directed APRV modality on a transport ventilator, adjusting T Low based on respiratory mechanics. This study demonstrated that CD-APRV can be safely used, with the advantage of guiding expiratory duration adjustments based on physiologic feedback from the lungs.