To estimate the incremental cost-effectiveness of a liver transplant program that utilizes normothermic machine perfusion (NMP) alongside static cold storage (SCS) compared to SCS alone (control). A Markov model compared strategies (NMP vs. control) using 1-year cycle lengths over a 5-year time horizon from the public healthcare payer perspective. Primary micro-costing data from a single center retrospective trial were applied along with utility values from literature sources. Transition probabilities were deduced using the retrospective trial cohort, local transplant data, and supplemented with literature values. Scenario and probabilistic sensitivity analysis (PSA) were conducted. The NMP strategy was cost-effective in comparison to the control strategy, which was dominated. The mean cost for NMP was $456 455 (2021 US$) and the control was $519 222. The NMP strategy had greater incremental quality-adjusted life years (QALYs) gains over 5 years compared to the control, with 3.48 versus 3.17, respectively. The overarching results remained unchanged in scenario analysis. In PSA, NMP was cost-effective in 63% of iterations at a willingness-to-pay threshold of $40 941. The addition of NMP to a liver transplant program results in greater QALY gains and is cost-effective from the public healthcare payer perspective.

Enhanced Recovery After Surgery (ERAS) is a global surgical quality improvement program that involves evidence-based guidelines and implementation strategies designed to improve patient outcomes by engaging multidisciplinary care teams in surgical practice change.¹ An increasing body of evidence has demonstrated the effectiveness of systemwide implementation of ERAS in improving patient outcomes while achieving cost savings in colorectal surgery^2-5 and other disciplines.⁶ Benefits include decreased hospital length of stay (LOS) and decreased complications, with no significant increase in readmission or mortality rates.¹ Economic evaluation of ERAS has demonstrated its cost-effectiveness and supported expansion across surgical disciplines with return on investment ratios as high as 7.3.⁷

The use of sirolimus (SRL) in orthotopic liver transplantation (OLT) has been controversial after experimental data suggested an increased risk of hepatic artery thrombosis (HAT). To assess the safety and efficacy of SRL as de novo immunosuppression in OLT recipients. Outcomes of 252 OLT patients who received SRL were compared with outcomes of 291 OLT recipients who received calcineurin inhibitor in a retrospective study. Primary outcomes of this study were: patient- and graft survivals, vascular, biliary, wound complications and rejection rates. Secondary outcomes were: postoperative infection rate, bone marrow and renal function and changes of lipid levels. Patient- and graft survivals, rejection and infection rates were similar. In the SRL group, HAT occurred in 1.2%, biliary complications in 19.4%, and incisional hernias in 9.1%. In the control group the incidence of HAT was 5.8% (P = 0.004), biliary complications 18.5% (P = NS) and incisional hernias 7.2% (P = NS). Patients on SRL experienced significantly higher levels of serum triglycerides but fewer acute cellular rejections. Bone marrow and renal functions were similar in both the groups. Our findings would suggest that SRL is safe and effective for very selected OLT recipients. Randomized controlled trials are necessary to confirm our results.

Background Liver transplantation is an effective treatment for end-stage liver disease. However, waiting lists continue to lengthen as demand exceeds supply. Use of extended criteria donors has helped but is associated with increased rates of complications. The application of normothermic machine perfusion (NMP) has been shown to be protective, especially in more marginal grafts. Despite this benefit, no cost-effectiveness studies have been published. Objective This study serves as a prelude to a cost-effectiveness analysis of the costs of liver procurement, transplantation, and machine perfusion in a Canadian setting. Methods The total costs were calculated for 106 in-province procurements, the set cost for 237 out-of-province procurements, and 343 liver transplantations. These costs include overheads, supplies, anaesthesia technologist and nursing salaries, and physician billings. Base and modified costs for all procedures were calculated, with consideration of physician billing modifiers. The total cost per run of NMP was calculated, with a range based on variations in the exchange rates for Great British pounds (₤) to Canadian dollars ($Can), year 2019 values. Results Costs were $Can30,770.22 for in-province and $Can44,636.73 for out-of-province liver procurement and transplantation. These increased to $Can35,659.22 and 48,076.18 when considering modifiers. The minimum cost per NMP run was $Can18,593.02. Conclusions Although the cost per run is substantial, NMP could potentially lead to cost savings by decreasing night-time salary premiums, complications, and patient length of stay. A formal cost-effectiveness study of NMP in liver transplantation is underway to help clarify the financial benefit or burden of this new technology.

Vasopressin is an essential hormone involved in the maintenance of cardiovascular homeostasis. It has been in use therapeutically for many decades, with an emphasis on its vasoconstrictive and antidiuretic properties. However, this hormone has a ubiquitous influence and has specific effects on the heart. Although difficult to separate from its powerful vascular effects in the clinical setting, a better understanding of vasopressin's direct cardiac effects could lead to its more effective clinical use for a variety of shock states by maximizing its therapeutic benefit. The cardiac-specific effects of vasopressin are complex and require further elucidation. Complicating our understanding include the various receptors and secondary messengers involved in vasopressin's effects, which may lead to various results based on differing doses and varying environmental conditions. Thus, there have been contradictory reports on vasopressin's action on the coronary vasculature and on its effect on inotropy. However, beneficial results have been found and warrant further study to expand the potential therapeutic role of vasopressin. This review outlines the effect of vasopressin on the coronary vasculature, cardiac contractility, and on hypertrophy and cardioprotection. These cardiac-specific effects of vasopressin represent an interesting area for further study for potentially important therapeutic benefits.

Normothermic machine perfusion (NMP) has emerged as a valuable tool in the preservation of liver allografts before transplantation. Randomized trials have shown that replacing static cold storage (SCS) with NMP reduces allograft injury and improves graft utilization. The University of Alberta's liver transplant program was one of the early adopters of NMP in North America. Herein, we describe our seven-year experience applying NMP to extend preservation time in liver transplantation using a 'back-to-base' approach. From 2015 to 2021, 79 livers were transplanted following NMP compared to 386 after SCS only. NMP livers were preserved for a median time of 847min compared to 288.5min in the SCS cohort (p<0.0001). Despite this, we observed significantly improved 30-day graft survival (p=0.030), though no differences in long term patient survival, major complications or biliary or vascular complications. We also found that while SCS time was strongly associated with increased graft failure at one year in the SCS cohort (p=0.006), there was no such association amongst NMP livers (p=0.171). Our experience suggests that NMP can safely extend the total preservation time of liver allografts without increasing complications.