Tolerable Duration of Warm Ischaemia After Circulatory Death Is Safe For At Least One Hour in Porcine Lungs: Functional Assessment with Ex Vivo Lung Perfusion.

BACKGROUND: Lungs from donation after circulatory death (DCD) may be an underused resource for transplantation. The aim was to investigate, with a DCD pig model, if it was possible to recondition lungs exposed for up to 2 h of warm ischaemia with ex vivo lung perfusion (EVLP). METHODS: Danish domestic pigs (N = 17) were randomized into three groups. In the two study groups, lungs were exposed to either 1 or 2 h of warm ischaemia. All lungs were reconditioned and evaluated after 83 ± 38 minutes of perfusion at FiO2 1.0 and 0.21 with EVLP. Outcome measures were gas exchange, pulmonary physiology, inflammatory markers, and histopathologic assessment score. RESULTS: Lungs exposed for 2 h of warm ischaemia did not meet the criteria: PaO2 > 13 kPa required for donation compared with lungs subjected to 0 and 1 h of warm ischaemia (11.0 kPa vs. 14.2 kPa, P < 0.001). These lungs also developed an increased amount of foam and fluid in the airways. No differences in PaCO2, compliance, or pulmonary vascular resistance were observed. CONCLUSION: Results show that while lungs subjected to 0 or 1 h of warm ischaemia meet the criteria for transplantation based on EVLP evaluation, lungs subjected to 2 h of warm ischaemia did not.

Transplantation of High-risk Donor Livers After Ex Situ Resuscitation and Assessment Using Combined Hypo- and Normothermic Machine Perfusion: A Prospective Clinical Trial.

OBJECTIVE: The aim of this study was to evaluate sequential hypothermic and normothermic machine perfusion (NMP) as a tool to resuscitate and assess viability of initially declined donor livers to enable safe transplantation. SUMMARY BACKGROUND DATA: Machine perfusion is increasingly used to resuscitate and test the function of donor livers. Although (dual) hypothermic oxygenated machine perfusion ([D]HOPE) resuscitates livers after cold storage, NMP enables assessment of hepatobiliary function. METHODS: In a prospective clinical trial, nationwide declined livers were subjected to ex situ NMP (viability assessment phase), preceded by 1-hour DHOPE (resuscitation phase) and 1 hour of controlled oxygenated rewarming (COR), using a perfusion fluid containing an hemoglobin-based oxygen carrier. During the first 2.5 hours of NMP, hepatobiliary viability was assessed, using predefined criteria: perfusate lactate <1.7 mmol/L, pH 7.35 to 7.45, bile production >10 mL, and bile pH >7.45. Livers meeting all criteria were accepted for transplantation. Primary endpoint was 3-month graft survival. RESULTS: Sixteen livers underwent DHOPE-COR-NMP. All livers were from donors after circulatory death, with median age of 63 (range 42-82) years and median Eurotransplant donor risk index of 2.82. During NMP, all livers cleared lactate and produced sufficient bile volume, but in 5 livers bile pH remained <7.45. The 11 (69%) livers that met all viability criteria were successfully transplanted, with 100% patient and graft survival at 3 and 6 months. Introduction of DHOPE-COR-NMP increased the number of deceased donor liver transplants by 20%. CONCLUSIONS: Sequential DHOPE-COR-NMP enabled resuscitation and safe selection of initially declined high-risk donor livers, thereby increasing the number of transplantable livers by 20%. TRIAL REGISTRATION: www.trialregister.nl; NTR5972.

Normothermic Perfusion in the Assessment and Preservation of Declined Livers Before Transplantation: Hyperoxia and Vasoplegia-Important Lessons From the First 12 Cases.

BACKGROUND: A program of normothermic ex situ liver perfusion (NESLiP) was developed to facilitate better assessment and use of marginal livers, while minimizing cold ischemia. METHODS: Declined marginal livers and those offered for research were evaluated. Normothermic ex situ liver perfusion was performed using an erythrocyte-based perfusate. Viability was assessed with reference to biochemical changes in the perfusate. RESULTS: Twelve livers (9 donation after circulatory death [DCD] and 3 from brain-dead donors), median Donor Risk Index 2.15, were subjected to NESLiP for a median 284 minutes (range, 122-530 minutes) after an initial cold storage period of 427 minutes (range, 222-877 minutes). The first 6 livers were perfused at high perfusate oxygen tensions, and the subsequent 6 at near-physiologic oxygen tensions. After transplantation, 5 of the first 6 recipients developed postreperfusion syndrome and 4 had sustained vasoplegia; 1 recipient experienced primary nonfunction in conjunction with a difficult explant. The subsequent 6 liver transplants, with livers perfused at lower oxygen tensions, reperfused uneventfully. Three DCD liver recipients developed cholangiopathy, and this was associated with an inability to produce an alkali bile during NESLiP. CONCLUSIONS: Normothermic ex situ liver perfusion enabled assessment and transplantation of 12 livers that may otherwise not have been used. Avoidance of hyperoxia during perfusion may prevent postreperfusion syndrome and vasoplegia, and monitoring biliary pH, rather than absolute bile production, may be important in determining the likelihood of posttransplant cholangiopathy. Normothermic ex situ liver perfusion has the potential to increase liver utilization, but more work is required to define factors predicting good outcomes.

Correlation between PaO2/FiO2 and airway and vascular parameters in the assessment of cellular ex vivo lung perfusion system.

BACKGROUND: Ex vivo lung perfusion (EVLP) may be an essential process for the pre-transplant evaluation of the donor lungs. Currently, the partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2, or PF) ratio is the standard in the assessment of lung function in cellular EVLP, whereas other parameters, including airway and vascular parameters, have only been partially utilized. The primary purpose of this study is to assess the potential utility of other parameters as a surrogate of lung function in EVLP. METHODS: Yorkshire swine lungs (n = 12) and rejected human donor lungs (n = 12) were perfused in cellular-based EVLP for 2 hours. PF ratio, airway parameters (peak airway pressure, plateau pressure, dynamic compliance and static compliance) and vascular parameters (pulmonary vascular resistance and pulmonary artery pressure) were measured. The correlations between PF ratio and one of these parameters were analyzed. RESULTS: Correlations were identified in the following combinations: PF ratio and airway parameters (p < 0.05, each); PF ratio and vascular parameters (p < 0.05, each); static compliance and pulmonary vascular resistance in swine lungs (p = 0.0001); and PF ratio and airway parameters in rejected human lungs (p < 0.05, each). There were significant differences in all parameters between suitable cases and non-suitable cases in swine lungs (p < 0.02, each). CONCLUSIONS: Our results show that airway parameters are complementary quantitative indicators of lung function in cellular EVLP, based on the correlations with PF ratio in both swine lungs and human lungs.

Effect of warm ischemia on renal function during partial nephrectomy: assessment with new 99mTc-mercaptoacetyltriglycine scintigraphy parameter.

OBJECTIVE: A decrease in renal function after partial nephrectomy caused by ischemic damage or nephron loss cannot be distinguished by conventional methods. We quantified renal function using a new 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) renal scintigraphy parameter. MATERIAL AND METHODS: We included 32 patients with a normally functioning contralateral kidney who received open partial nephrectomy with average warm ischemic time of 26.0 (range 14-46) min in this study. Effective renal plasma flow (ERPF) was calculated from 99mTc-MAG3 renal scintigraphy before and at 1 week and 6 months after surgery. We also analyzed regional 99mTc-MAG3 uptake in the surgically nonaffected parts. RESULTS: One week after surgery, average ERPF in the operated kidney decreased to 66.4% from baseline (from 177.8 to 116.9 mL/min/1.73 m2) and regional 99mTc-MAG3 uptake decreased to 83.4%. A stronger correlation was found between ischemic time and the decrease in regional 99mTc-MAG3 uptake (P<.001) compared with ERPF (P=.029). The decrease in regional 99mTc-MAG3 uptake remained at 6 months in the group with ischemic time≥25 minutes, whereas it recovered when ischemic time was <25 minutes. CONCLUSION: This new parameter quantified ischemic renal damage better than the conventional split functional evaluation. When warm ischemic time was ≥25 minutes, irreversible diffuse damage was seen in surgically preserved nephrons.