Normothermic machine perfusion of donor-lungs ex-vivo: promoting clinical adoption

Abstract

Purpose of review Lung transplantation offers the only realistic therapeutic option for patients with end-stage lung disease. However, this is impacted by a shortfall in availability of suitable donor-lungs. Normothermic machine perfusion of donor-lungs outside the donor body also known as ex-vivo lung perfusion (EVLP) offers a potential solution through objective assessment, reconditioning and treatment of donor-lungs initially deemed unsuitable for use. This review discusses key advances and challenges in the wider clinical adoption of this technology. Recent findings This review will summarize key research within the following areas: recent clinical trials utilizing EVLP, logistical challenges, EVLP protocol innovations, novel assessment methods and current research into therapeutic modulation of lung function during EVLP. Summary Normothermic machine perfusion of donor-lungs ex-vivo offers a promising platform to assess and modulate donor-lung quality prior to transplantation. Consensus on how and when to best utilize EVLP is yet to be reached, meaning that widespread clinical adoption of the technology has not yet become a reality. Further work is needed on agreed indications, perfusion protocols and organization of services before becoming a regularly used procedure prior to lung transplantation.

Normothermic Machine Perfusion in pediatric liver transplantation: A survey of attitudes and barriers

“…The implementation of NMP in adult lung transplantation, where similar difficulties reallocating organs once procurement has begun exist, has shown much promise 11 . OPOs and organ management teams with expertise in NMP technology have worked closely to coordinate efforts and this has allowed successful utilization of lungs in clinical transplantation that would previously have been discarded 12 . Implementation of a similar strategy in pediatric liver transplantation could promote national reallocation even after cross‐clamp and completion of organ procurement.…”

“…has allowed successful utilization of lungs in clinical transplantation that would previously have been discarded. 12 Implementation of a similar strategy in pediatric liver transplantation could promote national reallocation even after cross-clamp and completion of organ procurement.…”

Novel approaches for long-term lung transplant survival

“…Perhaps the most significant advantage of EVLP relates to its use as a therapeutic platform for administration of localized, targeted lung-specific therapies ( 61 , 65 , 66 ). Even without modifications, EVLP is associated with alterations in the donor lung environment from diminished release of inflammatory mediators and augmentation of anti-inflammatory signaling pathways ( 67 – 70 ).…”

Ex Vivo Lung Perfusion: A Platform for Donor Lung Assessment, Treatment and Recovery

“…Typically positive airway pressure ventilation is carried out although negative pressure ventilation is being explored [11]. The perfusion fluid consists of highly oncotic dextrancontaining Steen solution or equivalent ± supplementation with blood products [12]. Pulmonary venous output collects in the reservoir and is pumped through the circuit by a centrifugal pump, passing through a heat exchanger which maintains normothermia, then a membrane gas exchanger and leucocyte filter before its pressurised return to the pulmonary arteries (see Figure 1).…”

“…Both human and animal (porcine and murine) models have been employed experimentally. A lack of standardisation has led to difficulties in data comparison [12]. pulmonary arteries (see Figure 1).…”