A comparison of hemodynamic measurement methods during orthotopic liver transplantation: evaluating agreement and trending ability of PiCCO versus pulmonary artery catheter techniques.

BACKGROUND: Significant hemodynamic changes occur during liver transplantation, emphasizing the importance of precious and continuous monitoring of cardiac output, cardiac index, and other parameters. Although the monitoring of cardiac output by pulse indicator continuous cardiac output (PiCCO) was statistically homogeneous compared to the clinical gold standard pulmonary artery catheterization (PAC) in previous studies of liver transplantation, there are fewer statistical methods for the assessment of its conclusions, and a lack of comparisons of other hemodynamic parameters (e.g., SVRI, systemic vascular resistance index). Some studies have also concluded that the agreement between PiCCO and PAC is not good enough. Overall, there are no uniform conclusions regarding the agreement between PiCCO and PAC in previous studies. This study evaluates the agreement and trending ability of relevant hemodynamic parameters obtained with PiCCO compared to the clinical gold standard PAC from multiple perspectives, employing various statistical methods. METHODS: Fifty-two liver transplantation patients were included. Cardiac output (CO), cardiac index (CI), SVRI and stroke volume index (SVI) values were monitored at eight time points using both PiCCO and PAC. The results were analyzed by Bland-Altman analysis, Passing-bablok regression, intra-class correlation coefficient (ICC), 4-quadrant plot, polar plot, and trend interchangeability method (TIM). RESULTS: The Bland-Altman analysis revealed high percentage errors for PiCCO: 54.06% for CO, 52.70% for CI, 62.18% for SVRI, and 51.97% for SVI, indicating poor accuracy. While Passing-Bablok plots showed favorable agreement for SVRI overall and during various phases, the agreement for other parameters was less satisfactory. The ICC results confirmed good overall agreement between the two devices across most parameters, except for SVRI during the new liver phase, which showed poor agreement. Additionally, four-quadrant and polar plot analyses indicated that all agreement rate values fell below the clinically acceptable threshold of over 90%, and all angular deviation values exceeded ± 5°, demonstrating that PiCCO is unable to meet the acceptable trends. Using the TIM, the interchangeability rates were found to be quite low: 20% for CO and CI, 16% for SVRI, and 13% for SVI. CONCLUSIONS: Our study revealed notable disparities in absolute values of CO, CI, SVRI and SVI between PiCCO and PAC in intraoperative liver transplant settings, notably during the neohepatic phase where errors were particularly pronounced. Consequently, these findings highlight the need for careful consideration of PiCCO's advantages and disadvantages in liver transplantation scenarios, including its multiple parameters (such as the encompassing extravascular lung water index), against its limited correlation with PAC.

A randomized-controlled trial of ischemia-free liver transplantation for end-stage liver disease.

BACKGROUND & AIMS: Ischemia-reperfusion injury (IRI) has thus far been considered as an inevitable component of organ transplantation, compromising outcomes, and limiting organ availability. Ischemia-free organ transplantation is a novel approach designed to avoid IRI, with the potential to improve outcomes. METHODS: In this randomized-controlled clinical trial, recipients of livers from donors after brain death were randomly assigned to receive either an ischemia-free or a 'conventional' transplant. The primary endpoint was the incidence of early allograft dysfunction. Secondary endpoints included complications related to graft IRI. RESULTS: Out of 68 randomized patients, 65 underwent transplants and were included in the analysis. 32 patients received ischemia-free liver transplantation (IFLT), and 33 received conventional liver transplantation (CLT). Early allograft dysfunction occurred in two recipients (6%) randomized to IFLT and in eight (24%) randomized to CLT (difference -18%; 95% CI -35% to -1%; p = 0.044). Post-reperfusion syndrome occurred in three recipients (9%) randomized to IFLT and in 21 (64%) randomized to CLT (difference -54%; 95% CI -74% to -35%; p <0.001). Non-anastomotic biliary strictures diagnosed with protocol magnetic resonance cholangiopancreatography at 12 months were observed in two recipients (8%) randomized to IFLT and in nine (36%) randomized to CLT (difference, -28%; 95% CI -50% to -7%; p = 0.014). The comprehensive complication index at 1 year after transplantation was 30.48 (95% CI 23.25-37.71) in the IFLT group vs. 42.14 (95% CI 35.01-49.26) in the CLT group (difference -11.66; 95% CI -21.81 to -1.51; p = 0.025). CONCLUSIONS: Among patients with end-stage liver disease, IFLT significantly reduced complications related to IRI compared to a conventional approach. CLINICAL TRIAL REGISTRATION: chictr.org. ChiCTR1900021158. IMPACT AND IMPLICATIONS: Ischemia-reperfusion injury has thus far been considered as an inevitable event in organ transplantation, compromising outcomes and limiting organ availability. Ischemia-free liver transplantation is a novel approach of transplanting donor livers without interruption of blood supply. We showed that in patients with end-stage liver disease, ischemia-free liver transplantation, compared with a conventional approach, led to reduced complications related to ischemia-reperfusion injury in this randomized trial. This new approach is expected to change the current practice in organ transplantation, improving transplant outcomes, increasing organ utilization, while providing a clinical model to delineate the impact of organ injury on alloimmunity.

Ischaemia-free liver transplantation in humans: a first-in-human trial.

Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences. Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT). Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach. Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers. Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology. Panel: Research in context.

Association of Perfusion Characteristics and Posttransplant Liver Function in Ischemia-Free Liver Transplantation.

It has been shown that normothermic machine perfusion (NMP), a novel preservation method, is able to assess and resuscitate liver grafts with risk factors. However, there is no consistent criteria for the assessment of liver grafts with NMP. Ischemia-free liver transplantation (IFLT) includes innovative surgical techniques and NMP, which can protect liver grafts from ischemia throughout organ procurement, preservation, and implantation. In our center, 28 human livers from donation after brain death donors were subjected to IFLT between July 2017 and October 2018. The correlation between posttransplant liver function tests with the perfusion parameters, blood gas analysis of perfusate, and bile biochemistry were analyzed. During the preservation phase, the vascular flow was stable, and the lactate level decreased rapidly. The transaminase release in the perfusate was low but stable, whereas the glucose level remained high. The perfusate lactate and aspartate aminotransferase (AST) levels at 1 hour of perfusion were correlated with the posttransplant peak AST level. There were negative correlations between the portal vein and hepatic artery flows at the end of perfusion and the peak transaminase levels within 7 days after transplantation. In conclusion, during IFLT, NMP is able to bridge the liver grafts from donors to recipients and can allow the assessment of liver function by perfusion characteristics.

Prospective, single-centre, randomised controlled trial to evaluate the efficacy and safety of ischaemia-free liver transplantation (IFLT) in the treatment of end-stage liver disease.

INTRODUCTION: During conventional liver transplantation (CLT), ischaemia-reperfusion injury (IRI) is inevitable and is associated with complications such as early allograft dysfunction (EAD), primary non-function and ischaemic-type biliary lesions. We have established a novel procedure called ischaemia-free liver transplantation (IFLT). The results from a pilot study suggest that IFLT might prevent IRI and yield better transplant outcomes than CLT. The purpose of this study was to further assess the efficacy and safety of IFLT versus CLT in patients with end-stage liver disease. METHODS AND ANALYSIS: This is an investigator-initiated, open-label, phase III, prospective, single-centre randomised controlled trial on the effects of IFLT in patients with end-stage liver disease. Adult patients (aged 18-75 years) eligible for liver transplantation will be screened for participation in this trial and will be randomised between the IFLT group (n=34) and the CLT group (n=34). In the IFLT group, the donor liver will be procured, preserved and implanted with continuous normothermic machine perfusion (NMP). In the CLT group, the donor liver will be procured after a fast cold flush, preserved in 0°C-4°C solution and implanted under hypothermic and hypoxic conditions. Patients in both groups will be managed according to the standard protocol of our centre. The primary end point is the incidence of EAD after liver transplantation. Intraoperative and postoperative parameters of donor livers and recipients will be observed and recorded, and postoperative liver graft function, complications and recipient and graft survival will be evaluated. After a 12-month follow-up of the last enrolled recipient, the outcomes will be analysed to evaluate the safety and efficacy of IFLT versus CLT in patients with end-stage liver disease. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Sun Yat-sen University. The findings will be disseminated to the public through conference presentations and peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: ChiCTR1900021158.