Airway pressure release ventilation during ex vivo lung perfusion attenuates injury

Abstract

Objective Critical organ shortages have resulted in Ex Vivo Lung Perfusion (EVLP) gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of Donation after Circulatory Death (DCD) organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation (APRV) during EVLP improves lung function after transplantation. Methods Two groups (n=4 animals/group) of porcine DCD donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of EVLP rehabilitation with either standard conventional volume-based ventilation or pressure-based APRV. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for PaO2/FiO2 ratios, airway pressures for calculation of compliance, and percent wet weight gain during EVLP and reperfusion were measured. Results APRV during EVLP significantly improved left-lung oxygenation at 2-hours (561.5±83.9 vs 341.1±136.1 mmHg) and 4-hours (569.1±18.3 vs 463.5±78.4 mmHg). Similarly, compliance was significantly higher at 2-hours (26.0±5.2 vs 15.0±4.6 mL/cmH2O) and 4-hours (30.6±1.3 vs 17.7±5.9 mL/cmH2O) after transplantation. Finally, APRV significantly reduced lung edema development on EVLP based on percentage weight gain (36.9±14.6 vs 73.9±4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. Conclusions Pressure-directed APRV ventilation strategy during EVLP improves rehabilitation of severely injured DCD lungs. After transplant these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared to lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical EVLP protocols, could advance the field of DCD lung rehabilitation to expand the lung donor pool.

Reduced-flow ex vivo lung perfusion to rehabilitate lungs donated after circulatory death

“…Alternative ventilation strategies, attenuation of ischemia-reperfusion injury, modulation of innate immunity, and targeted protein and gene therapy will all be necessary components of successful lung repair, but this must be accomplished on a lung protective platform such as EVLP, which may benefit from lower perfusion flow rates. 6,7,9,34,36,37 Moving forward, these results should be applied in future laboratory and clinical experimental designs. We believe the next logical place to incorporate these findings is in the rehabilitation of lungs that are extremely high-risk or have shown early signs of deterioration when initiated on EVLP.…”

“…A porcine donation after circulatory death (DCD) and EVLP model was utilized as previously performed by our laboratory with minor modifications as indicated. 9,16 Animals were sedated and intubated. General anesthesia was maintained while animals were ventilated with 100% oxygen to measure baseline parameters.…”

Randomized Feasibility Trial of a Low Tidal Volume-Airway Pressure Release Ventilation Protocol Compared With Traditional Airway Pressure Release Ventilation and Volume Control Ventilation Protocols

“…The mortality benefits of APRV remain unproven. APRV appears to improve oxygenation or Pa o 2 /F io 2 ratio in patients with hypoxemic respiratory failure ( 5 , 16 , 32 – 42 ). Although clinicians often titrate mechanical ventilation to optimize oxygenation, LTV is what confers mortality benefit, not improvement in oxygenation ( 1 ).…”

Evolving Trend of EVLP: Advancements and Emerging Pathways

“…When procuring lungs from an uncontrolled donor after circulatory determination of death following an extended period of warm ischemia, EVLP with continuous positive airway pressure, and protective mechanical ventilation could get a satisfactory result after 6 months of surgery [109]. Pressuredirected airway pressure release ventilation strategy showed to have more benefit for rehabilitation of severe injury [110].…”