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Normothermic Machine Perfusion Enhances Intraoperative Hepatocellular Synthetic Capacity

A Propensity Score-matched Analysis

Ionescu, Mihnea-Ioan MD1; Tillakaratne, Suchintha1; Hodson, James2; Gunson, Bridget3; Nasralla, David4; Pinter Carvalheiro da Silva Boteon, Amanda MD1; Sermon, Kate1; Mergental, Hynek FRCS1; Isaac, John R. MBBS, MD, FRCS1; Roberts, John K.1; Muiesan, Paolo FRCS1; Friend, Peter4; Mirza, Darius F.1; Bennett, Davinia5; Perera, M. Thamara P.R. MBBS, FRCS, PhD1

doi: 10.1097/TP.0000000000002720
Original Clinical Science—Liver
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Background. Normothermic machine perfusion (NMP) of liver grafts is increasingly being incorporated in clinical practice. Current evidence has shown NMP plays a role in reconditioning the synthetic and energy capabilities of grafts. Intraoperative coagulation profile is a surrogate of graft quality and preservation status; however, to date this aspect has not been documented.

Methods. The liver transplantation recipients who received NMP liver grafts in the QEHB between 2013 and 2016 were compared in terms of intraoperative thromboelastography characteristics (R time, K time, α-angle, maximum amplitude, G value, and LY30) to a propensity score-matched control group, where the grafts were preserved by traditional static cold storage (SCS).

Results. After propensity matching, none of the thromboelastography characteristics were found to differ significantly between the 72 pairs of SCS and NMP organs when measured preimplantation. However, postimplantation, NMP organs had significantly shorter K time (median: 2.8 vs 3.6 min, P = 0.010) and R + K time (11.4 vs 13.7 min, P = 0.016), as well as significantly larger α-angle (55.9° vs 44.8°, P = 0.002), maximum amplitude (53.5 vs 49.6 mm, P = 0.044), and G values (5.8 vs 4.9k dynes/cm2, P = 0.043) than SCS organs. Hyperfibrinolysis after implantation was also mitigated by NMP, with fewer patients requiring aggressive factor correction during surgery (LY30 = 0, NMP vs SCS: 83% vs 60%, P = 0.004). Consequently, NMP organs required significantly fewer platelet units to be transfused during the transplant procedure (median: 0 vs 5, P = 0.001).

Conclusions. In this study, we have shown that NMP liver grafts return better coagulation profiles intraoperatively, which could be attributed to the preservation of liver grafts under physiological conditions.

1 The Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.

2 Institute of Translational Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.

3 National Institute for Health Research (NIHR), Birmingham Biomedical Research Centre (BRC), Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.

4 Oxford Transplant Centre, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.

5 Department of Anaesthesia and Critical Care, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.

Received 13 September 2018. Revision received 6 March 2019.

Accepted 8 March 2019.

Clinical Trial notation: This retrospective study was approved by the Clinical Audit and Research Management System (CARMS) of the University Hospitals Birmingham NHS Foundation Trust (registration number: CARMS-14049).

Peter Friend is a co-founder, Chief Medical Officer, and stock-holder in OrganOx Ltd. David Nasralla has received consultancy payments from OrganOx Ltd. There are no conflicts of interest from any other authors with regard to the contents and study subjects or technology.

The authors declare no funding for this article.

M.-I.I., D.B., and M.T.P.R.P. wrote the article. M.-I.I., S.T., B.G., A.P.C.S.B., and K.S. collected the data. J.H. performed statistical analysis. M.-I.I., M.T.P.R.P., H.M., D.N., J.R.I., J.K.R., P.M., P.F., D.F.M., and D.B. performed data analysis. M.T.P.R.P., H.M., D.N., J.R.I., J.K.R., P.M., P.F., D.F.M., and D.B. contributed to data interpretation and intellectual content. M.T.P.R.P. is the lead author of this article and contributed to the concept of this article.

Correspondence: M. Thamara P. R. Perera, MBBS, FRCS, PhD, Consultant Transplant Surgeon, The Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham B15 2TH, United Kingdom. (thamara.perera@uhb.nhs.uk).

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