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Clinical transplantation using negative pressure ventilation ex situ lung perfusion with extended criteria donor lungs.

ABSTRACT: Lung transplantation remains the best treatment option for end-stage lung disease; however, is limited by a shortage of donor grafts. Ex situ lung perfusion, also known as ex vivo lung perfusion, has been shown to allow for the safe evaluation and reconditioning of extended criteria donor lungs, increasing donor utilization. Negative pressure ventilation ex situ lung perfusion has been shown, preclinically, to result in less ventilator-induced lung injury than positive pressure ventilation. Here we demonstrate that, in a single-arm interventional study (ClinicalTrials.gov number NCT03293043) of 12 extended criteria donor human lungs, negative pressure ventilation ex situ lung perfusion allows for preservation and evaluation of donor lungs with all grafts and patients surviving to 30 days and recovered to discharge from hospital. This trial also demonstrates that ex situ lung perfusion is safe and feasible with no patients demonstrating primary graft dysfunction scores grade 3 at 72?h or requiring post-operative extracorporeal membrane oxygenation.

SUBMITTER: Buchko MT

PROVIDER: S-EPMC7666579 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Clinical transplantation using negative pressure ventilation ex situ lung perfusion with extended criteria donor lungs.

Buchko Max T MT Boroumand Nasim N Cheng Jeffrey C JC Hirji Alim A Halloran Kieran K Freed Darren H DH Nagendran Jayan J

Nature communications 20201113 1

Lung transplantation remains the best treatment option for end-stage lung disease; however, is limited by a shortage of donor grafts. Ex situ lung perfusion, also known as ex vivo lung perfusion, has been shown to allow for the safe evaluation and reconditioning of extended criteria donor lungs, increasing donor utilization. Negative pressure ventilation ex situ lung perfusion has been shown, preclinically, to result in less ventilator-induced lung injury than positive pressure ventilation. Here ...[more]

PMID: 33188221

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Project description:OBJECTIVE:Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. METHODS:Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured. RESULTS:Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2O vs 15.0 ± 4.6 mL/cm H2O) and 4 hours (30.6 ± 1.3 mL/cm H2O vs 17.7 ± 5.9 mL/cm H2O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of 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 airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.

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Clinical transplantation using negative pressure ventilation ex situ lung perfusion with extended criteria donor lungs.

Publications

Clinical transplantation using negative pressure ventilation ex situ lung perfusion with extended criteria donor lungs.

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