{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T22:17:51Z","timestamp":1785881871675,"version":"3.56.0"},"reference-count":22,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Controlled (c-) and uncontrolled (u-) DCDs are two entirely different types of donors, mainly because the duration of ischemic and reperfusion injury differs between them. We hypothesized that normothermic regional perfusion (NRP) management and performance (as indicated by the dynamic changes in blood flow and lactate) might be different in uDCDs and in cDCDs. Methods: We assessed 99 DCD donors that were consecutively evaluated by the Tuscany Regional Transplant Center from 2020 to 2024 (multi-center investigation), focusing on the comparison between NRP performance and management in uDCDs (n = 44) vs. cDCDs (n = 45). Results: NRP duration was significantly higher in uDCDs compared to cDCDs (p = 0.001). During NRP, we observed no changes in lactate values in uDCDs and cDCDs, a significant increase in transaminases, and a progressive reduction in NRP blood flow rates despite the administration of more fluids. Throughout the entire NRP duration, pH values were significantly lower and glucose levels were higher in uDCDs compared to cDCDs, even though a higher dosage of bicarbonate and insulin units were administered in uDCDs. Conclusions: In our series, we documented that NRP performance and management differed in uDCDs compared to cDCDs. This phenomenon may be mainly related to the different duration of the ischemic injury between these two types of donors. During NRP, uncontrolled DCDs showed a more severe metabolic derangement, which was only partially reversable by a more aggressive treatment (higher fluid volumes, insulin and bicarbonate dosages). Our results strongly suggest that there is likely space for optimization of NRP management in DCDs. Further research should address this issue, considering the disparity between the supply of organs and increasing transplantation needs.<\/jats:p>","DOI":"10.3390\/jcm14197053","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T15:05:06Z","timestamp":1759763106000},"page":"7053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Management of Normothermic Regional Perfusion Performance in Uncontrolled Versus Controlled Donation After Circulatory Death: A Multi-Center Investigation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0131-4450","authenticated-orcid":false,"given":"Chiara","family":"Lazzeri","sequence":"first","affiliation":[{"name":"Regional Transplant Center, 50135 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7933-8941","authenticated-orcid":false,"given":"Davide","family":"Ghinolfi","sequence":"additional","affiliation":[{"name":"Division of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Bonizzoli","sequence":"additional","affiliation":[{"name":"ICU and ECMO Center, Azienda Ospedaliero Universitaria Careggi, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Cultrera","sequence":"additional","affiliation":[{"name":"Coordinamento AV Centro, 50134 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Lo Pane","sequence":"additional","affiliation":[{"name":"Coordinamento Locale, 50100 Livorno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6075-175X","authenticated-orcid":false,"given":"Arianna","family":"Trizzino","sequence":"additional","affiliation":[{"name":"Division of Hepatic Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Precisi o Procissi","sequence":"additional","affiliation":[{"name":"Coordinamento Area Vasta Nord Ovest, 56121 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6807-0275","authenticated-orcid":false,"given":"Giuseppe","family":"Feltrin","sequence":"additional","affiliation":[{"name":"Italian National Transplant Center, 00162 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Peris","sequence":"additional","affiliation":[{"name":"Regional Transplant Center, 50135 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.jhep.2023.04.008","article-title":"Donation after circulatory death: Novel strategies to improve the liver transplant outcome","volume":"78","author":"Muiesan","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/tri.13506","article-title":"Donation after circulatory death today: An updated overview of the European landscape","volume":"33","author":"Lomero","year":"2020","journal-title":"Transplant. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1111\/ajt.16899","article-title":"Abdominal normothermic regional perfusion in controlled DCD liver transplantation: Outcomes and risk factors for graft loss","volume":"22","author":"Hessheimer","year":"2022","journal-title":"Am. J. Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1111\/tri.14121","article-title":"A systematic review and meta-analysis of regional perfusion in donation after circulatory death solid organ transplantation","volume":"34","author":"Vandendriessche","year":"2021","journal-title":"Transplant. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1111\/tri.13951","article-title":"Consensus statement on normothermic regional perfusion in donation after circulatory death: Report from the European Society for Organ Transplantation\u2019s Transplant Learning Journey","volume":"34","author":"Jochmans","year":"2021","journal-title":"Transplant. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1097\/TP.0000000000003345","article-title":"Abdominal normothermic regional perfusion in donation after circulatory death: A systematic review and critical appraisal","volume":"104","author":"Schurik","year":"2020","journal-title":"Transplantation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1097\/TP.0000000000005143","article-title":"Normothermic Regional Perfusion in Controlled Donation After the Circulatory Determination of Death: Understanding Where the Benefit Lies","volume":"109","author":"Minmabres","year":"2025","journal-title":"Transplantation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.23736\/S0375-9393.18.12635-6","article-title":"Implementing a donation after circulatory death program in a setting of donation after brain death activity","volume":"84","author":"Peris","year":"2018","journal-title":"Minerva Anestesiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lazzeri, C., Bonizzoli, M., Ghinolfi, D., Li Marzi, V., Luzzi, L., Entani Santini, L., and Peris, A. (2025). Uncontrolled Donation after circulatory death in the Tuscany Region: Evolving paradigms and potentials. A 8-year experience. Minerva Anestesiol, in press.","DOI":"10.23736\/S0375-9393.25.18475-7"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s13304-019-00640-5","article-title":"Past, present and future after circulatory death in Italy","volume":"71","author":"Muiesan","year":"2019","journal-title":"Updates Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e13896","DOI":"10.1111\/ctr.13896","article-title":"Utilization rate of uncontrolled donors after circulatory death- a 3- year single- center investigation","volume":"34","author":"Lazzeri","year":"2020","journal-title":"Clin. Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/lt.25899","article-title":"Sequential use of normothermic regional and ex situ machine perfusion in donation after circulatory death liver transplant","volume":"27","author":"Ghinolfi","year":"2020","journal-title":"Liver Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1097\/LVT.0000000000000122","article-title":"An extensive evaluation of hepatic markers of damage and regeneration in controlled and uncontrolled donation after circulatory death","volume":"29","author":"Basta","year":"2023","journal-title":"Liver Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.1016\/j.transproceed.2019.08.023","article-title":"Normothermic Regional Perfusion and Donation after circulatory death (controlled and uncontrolled): Metabolic differences and kidney transplantation","volume":"51","year":"2019","journal-title":"Transp. Proc."},{"key":"ref_15","first-page":"362","article-title":"Post-cardiac arrest syndrome","volume":"76","author":"Binks","year":"2010","journal-title":"Minerva Anestesiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lazzarin, T., Tonon, C.R., Martins, D., F\u00e1vero, E.L., Baumgratz, T.D., Pereira, F.W.L., Pinheiro, V.R., Ballarin, R.S., Queiroz, D.A.R., and Azevedo, P.S. (2022). Post-Cardiac Arrest: Mechanisms, Management, and Future Perspectives. J. Clin. Med., 12.","DOI":"10.3390\/jcm12010259"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4660","DOI":"10.1097\/LVT.0000000000000219","article-title":"Liver transplantation with uncontrolled versus controlled DCD donors using normothermic regional perfusion and ex-situ machine perfusion","volume":"30","author":"Ghinolfi","year":"2024","journal-title":"Liver Transplant."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/LVT.0000000000000267","article-title":"Liver transplantation from uncontrolled DCD donors-Is there light at the end of the tunnel?","volume":"30","author":"Vidgren","year":"2024","journal-title":"Liver Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tian, C., Wang, A., and Kuang, Y. (2025). Remote ischemic conditioning in experimental hepatic ischemia-reperfusion; A systematic and meta-analysis. Biomed. Rep., 22.","DOI":"10.3892\/br.2025.1927"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"533","DOI":"10.4254\/wjh.v13.i5.533","article-title":"Direct, remote and combined ischemic conditioning in liver surgery","volume":"13","author":"Stankiewicz","year":"2021","journal-title":"World J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1477-2574.2009.00006.x","article-title":"Effect of remote ischemic preconditioning on hepatic microcirculation and function in a rat model of hepatic ischemia reperfusion injury","volume":"11","author":"Tapuria","year":"2009","journal-title":"HPB"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1007\/s11605-009-0878-7","article-title":"Role of ischemic preconditioning in liver surgery and hepatic transplantation","volume":"13","author":"Urrutia","year":"2009","journal-title":"J. Gastrointest. Surg."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/19\/7053\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T15:29:37Z","timestamp":1759764577000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/19\/7053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,6]]},"references-count":22,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["jcm14197053"],"URL":"https:\/\/doi.org\/10.3390\/jcm14197053","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,6]]}}}