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The use of machine perfusion (MP) in liver transplantation (LT) is spreading worldwide. However, its efficacy has not been demonstrated, and its proper clinical use has far to go to be widely implemented. The Società Italiana Trapianti d’Organo (SITO) promoted the development of an evidence-based position paper. A 3-step approach has been adopted to develop this position paper. First, SITO appointed a chair and a cochair who then assembled a working group with specific experience of MP in LT. The Guideline Development Group framed the clinical questions into a patient, intervention, control, and outcome (PICO) format, extracted and analyzed the available literature, ranked the quality of the evidence, and prepared and graded the recommendations. Recommendations were then discussed by all the members of the SITO and were voted on via the Delphi method by an institutional review board. Finally, they were evaluated and scored by a panel of external reviewers. All available literature was analyzed, and its quality was ranked. A total of 18 recommendations regarding the use and the efficacy of ex situ hypothermic and normothermic machine perfusion and sequential normothermic regional perfusion and ex situ MP were prepared and graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. A critical and scientific approach is required for the safe implementation of this new technology.

Purpose We present the results of a clinical trial (NCT02061462) comparing outcomes after lung transplantation (LT) of subjects receiving lungs from donation after brain death (DBD) donors with that of subjects receiving lungs from donation after circulatory death (DCD) donors, procured using our original open lung strategy. Briefly, our protocol consists of a non-rapid normothermic open-lung procurement using recruitment manoeuvres, protective ventilation and CPAP without topical cooling. Methods We evaluated patients undergoing bilateral LT from 11/2014 to 07/2019; exclusion criteria: recipients ≤14 years, re-LT, donors ≥65 years, DCD category I and IV. Variables were prospectively recorded as well as respiratory functional parameters in the first year. Results We performed 143 LT; 22 cases were excluded, 121 were enrolled: 11 recipients received lungs from DCD donors (5 and 6 from DCD category II and III, respectively). The two groups had similar features. Most of the subjects had cystic fibrosis (72,7% and 61,9% of DCD and DBD, respectively). DCD donors’ BMI was significantly higher (p=0.022); 15,5% of DBD grafts underwent machine perfusion. Duration of postoperative mechanical ventilation was higher in the DCD group (DCD vs DBD=2 vs 1 day, p= 0.011). Incidence of grade 3 primary graft dysfunction was 27,3% in the DCD group and 18,2% in the DBD group (p=0.742). Cold ischemia and preservation times were significantly higher in the DCD group (p Conclusion Regardless of the small study population, our results are encouraging. Our data show the feasibility of LT from DCD donors using our original protocol, with adequate grafts function and survival.

The imbalance between the number of organ donors and the demand is currently a major health care problem, although improved technology and experience with long-term mechanical support are increasingly providing alternative solutions to end-stage heart disease. There are strict criteria to assess

Increasing numbers of trauma patients receive immediate and appropriate control of life-threatening injuries, but some of them eventually progress to brain death. Establishment of the best therapeutic strategies for patients with extensive and major trauma has led to significant improvement in donor conversion rates and increased utilization of deceased donors. Approximately 30% of all deceased organ donors are trauma patients who have suffered devastating neurologic injury and have progressed to brain death.

OBJECTIVES Donation after circulatory death (DCD) potentially provides transplantable lungs suitable for a transplant, but in Italy, the need for 20 min of a no-touch period after cardiac arrest for legal declaration of death poses real challenges to organ preservation. METHODS This is a single-institution, retrospective study using data collected prospectively between October and December 2017. After the approval of the multidisciplinary DCD study group of Regione Lombardia, Maastricht category III DCD donors became eligible for combined procurement of lungs and abdominal organs. Our group subsequently established a dedicated technical protocol. Our protocol consists of a non-rapid normothermic open-lung procurement process that takes place during abdominal normothermic regional perfusion, namely without pleural topical cooling before the start of pneumoplegia. After the lung is procured according to the technique described in the article, lung function is evaluated by ex vivo lung perfusion, which is run with the low-flow, open atrium, low haematocrit technique. RESULTS During the study, we managed 5 controlled DCDs. In 3 cases, the lungs were successfully transplanted. All 3 patients are alive after 1 year, with good respiratory function. CONCLUSIONS Our approach resulted in adequate lung preservation and successful transplants without detrimental effects on abdominal organ procurement, confirming the possibility of overcoming the obstacle of a long no-touch period in a DCD setting.

Background The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTX) is still being debated. Methods We performed a retrospective two-center analysis of the relationship between ECMO bridging duration and survival in 25 patients. Further survival analysis was obtained by dividing the patients according to waiting time on ECMO: up to 14 days (Early group) or longer (Late group). We also analyzed the impact of the ventilation strategy during ECMO bridging (ie, spontaneous breathing and noninvasive ventilation [NIV] or intubation and invasive mechanical ventilation [IMV]). Results Seventeen of 25 patients underwent a transplant (with a 76% 1-year survival), whereas eight patients died during bridging. In the 17 patients who underwent a transplant, mortality was positively related to waiting days until LTX (hazard ratio [HR], 1.12 per day; 95% CI, 1.02-1.23; P = .02), and the Early group showed better Kaplan-Meier curves (P = .02), higher 1-year survival rates (100% vs 50%, P = .03), and lower morbidity (days on IMV and length of stay in ICU and hospital). During the bridge to transplant, mortality increased steadily with time. Considering the overall outcome of the bridging program (25 patients), bridge duration adversely affected survival (HR, 1.06 per day; 95% CI, 1.01-1.11; P = .015) and 1-year survival (Early, 82% vs Late, 29%; P = .015). Morbidity indexes were lower in patients treated with NIV during the bridge. Conclusions The duration of the ECMO bridge is a relevant cofactor in the mortality and morbidity of critically ill patients awaiting organ allocation. The NIV strategy was associated with a less complicated clinical course after LTX.

The role of donation after cardiac death (DCD) in expanding the donor pool is mainly limited by the incidence of primary nonfunction (PNF) and ischemia-related complications. Even greater concern exists toward uncontrolled DCD, which represents the largest potential pool of DCD donors. We recently started the first Italian series of DCD liver transplantation, using normothermic regional perfusion (NRP) in 6 uncontrolled donors and in 1 controlled case to deal with the legally required no-touch period of 20 minutes. We examined our first 7 cases for the incidence of PNF, early graft dysfunction, and biliary complications. Acceptance of the graft was based on the trend of serum transaminase and lactate during NRP, the macroscopic appearance, and the liver biopsy. Hypothermic machine perfusion (HMP) was associated in selected cases to improve cold storage. Most notably, no cases of PNF were observed. Median posttransplant transaminase peak was 1014 IU/L (range, 393-3268 IU/L). Patient and graft survival were both 100% after a mean follow-up of 6.1 months (range, 3-9 months). No cases of ischemic cholangiopathy occurred during the follow-up. Only 1 anastomotic stricture completely resolved with endoscopic stenting. In conclusion, DCD liver transplantation is feasible in Italy despite the protracted no-touch period. The use of NRP and HMP seems to earn good graft function and proves safe in these organs. Liver Transplantation 23 166-173 2017 AASLD.

We appreciate Prof. Madias’s insightful comments on our paper and strong endorsement of our hypotheses [(1)][1]. He suggests additional potential solutions for better management of donors with dysfunctional hearts, including sympathetic activity monitoring, donor heart “nursing” with cardiac

The great potential of donation after cardiac death (DCD) in expanding the liver donor pool is limited by the inferior results due to the ischemic injury.1 Normothermic regional perfusion (NRP) and hypothermic machine perfusion (HMP) can improve the transplantation outcome.2,3 These technologies may

Organ transplantation is limited by the shortage of viable donor organs. Non-heart-beating donors (NHBD), also frequently referred to as donor after cardiac death (DCD), represent a promising source of grafts. Nevertheless, the initial period of warm ischemia can compromise the graft viability. Modified preservation techniques are crucial in stopping or reversing cellular injury, through cytoprotective mechanisms, allowing the recovery of a great portion of these grafts. Selective normothermic extracorporeal membrane oxygenation (NECMO) minimizes ischemic injury, playing a protective role on organ function preservation and maintaining tissue perfusion under controlled condition and temperature to restore metabolic processes. NECMO is believed to shift warm ischemic time toward ischemic preconditioning, providing greater viability for DCD donors. In the clinical setting, NECMO has been demonstrated to offer the possibility to obtain good quality grafts for transplant both in controlled and in uncontrolled DCD. Furthermore, in some countries ECMO has been used to support brain death (BD) multiorgan donors in case in which it is not possible to complete death assessment for cardiac or respiratory failure.

Pressure Support Ventilation (PSV) is a ventilatory mode designed to unload the respiratory muscles, while preserving the spontaneous respiratory activity of the patient [1]. FSV has been used both as a weaning technique and as a stand-alone ventilatory support mode in patients with acute respiratory failure [2,3].