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

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.

A Low-Cost Perfusate Alternative for Ex Vivo Lung Perfusion.

BACKGROUND: Normothermic ex vivo lung perfusion (EVLP) has been used successfully to evaluate and recondition marginal donor lungs; however, multiple barriers continue to prevent its widespread adoption. We sought to develop a common hospital ingredient-derived perfusate (CHIP) with equivalent functional and inflammatory characteristics to a standard Krebs-Henseleit buffer with 8% serum albumin-derived perfusate (KHB-Alb) to improve access and reduce costs of ex vivo organ perfusion. METHODS: Sixteen porcine lungs were perfused using negative pressure ventilation (NPV) EVLP for 12 hours in a normothermic state and were allocated equally to 2 groups: KHB-Alb vs CHIP. Physiological parameters, cytokine profiles, and edema formation were compared between treatment groups. RESULTS: Perfused lungs in both groups demonstrated equivalent oxygenation (partial pressure of arterial oxygen/fraction of inspired oxygen ratio >350 mm Hg) and physiological parameters. There was equivalent generation of tumor necrosis factor-α and IL-6, irrespective of perfusate solution used, when comparing CHIP vs KHB-Alb. Pig lungs developed equivalent edema formation between groups (CHIP: 15.8 ± 4.8%, KHB-Alb 19.5 ± 4.4%, P > .05). CONCLUSION: A perfusate derived of common hospital ingredients provides equivalent results to a standard Krebs-Henseleit buffer with 8% serum albumin-based perfusate in NPV-EVLP.

Total parenteral nutrition in ex vivo lung perfusion: Addressing metabolism improves both inflammation and oxygenation.

Ex vivo lung perfusion (EVLP) protocols generally limit metabolic supplementation to insulin and glucose. We sought to determine whether the addition of total parenteral nutrition (TPN) would improve lung function in EVLP. Ten porcine lungs were perfused using EVLP for 24 hours and supplemented with insulin and glucose. In the treatment group (n = 5), the perfusate was also supplemented with a continuous infusion of TPN containing lipids, amino acids, essential vitamins, and cofactors. Physiologic parameters and perfusate electrolytes were continuously evaluated. Perfusate lactate, lipid and branch chain amino acid (BCAA) concentrations were also analyzed to elucidate how substrates were being utilized over time. Lungs in the TPN group exhibited significantly better oxygenation. Perfusate sodium was more stable in the TPN group. In the control group, free fatty acids (FFA) were quickly depleted, reaching negligible levels early in the perfusion. Alternatively, BCAA in the control group rose continually over the perfusion demonstrating a shift toward proteolysis for energy substrate. In the TPN group, both FFA and BCAA concentrations remained stable at in vivo levels after initial stabilization. TNF-α concentrations were lower in the TPN group. The addition of TPN in EVLP allows for better electrolyte composition, decreased inflammation, and improved graft performance.

Continuous Hemodialysis Does Not Improve Graft Function During Ex Vivo Lung Perfusion Over 24 Hours.

BACKGROUND: Extended periods of ex vivo lung perfusion (EVLP) lead to several inadvertent consequences including accumulation of lactate and increasing electrolyte concentrations in the perfusate. We sought to determine whether continuous hemodialysis (CHD) of the perfusate would be a suitable modality for improving ionic homeostasis in extended EVLP without compromising functional outcomes. METHODS: Twelve porcine lungs were perfused using EVLP for 24 hours. All lungs were ventilated with negative pressure ventilation. Lungs in the treatment group (n = 6) underwent continuous hemodialysis of the perfusate. Functional parameters, edema formation, and histopathologic analysis were used to assess graft function. Electrolyte and lactate profiles were also followed to assess the efficiency of hemodialysis. RESULTS: Lungs in both treatment and control groups demonstrated stable and acceptable oxygenation to 24 hours. Lungs demonstrated a decrease in compliance over time. There was no difference in oxygenation and compliance between groups. CHD-EVLP lungs had higher pulmonary vascular resistance and pulmonary artery pressures. Despite increased perfusion pressures, weight gain at both 11 and 23 hours was not different between groups. Perfusate sodium and lactate concentrations were significantly lower in the CHD-EVLP group. CONCLUSION: The addition of continuous hemodialysis to EVLP did not improve graft function up to 24 hours despite improved maintenance of perfusate composition.