Preclinical validation of a customized circuit for ex situ uninterrupted cold-to-warm prolonged perfusion of the liver.

CONTEXT: Clinical adoption of ex situ liver perfusion is growing. While hypothermic perfusion protects against ischemia-reperfusion injury in marginal grafts, normothermic perfusion enables organ viability assessment and therefore selection of borderline grafts. The combination of hypothermic and normothermic perfusion, known as "cold-to-warm," may be the optimal sequence for organ preservation, but is difficult to achieve with most commercial perfusion systems. We developed an adaptable customized circuit allowing uninterrupted "cold-to-warm" perfusion and conducted preclinical studies on healthy porcine livers and discarded human livers to demonstrate the circuit's efficacy. METHODS: In collaboration with bioengineers, we developed a customized circuit that adapts to extracorporeal circulation consoles used in cardiovascular surgery and includes a proprietary reservoir enabling easy perfusate change without interrupting perfusion. This preclinical study was conducted on porcine and human livers. Perfusion parameters (pressures, flows, oxygenation) and organ viability were monitored. RESULTS: The customized circuit was adapted to a LivaNova S5® console, and the perfusions were flow-driven with real-time pressure monitoring. Ten porcine liver and 12 discarded human liver perfusions were performed during 14 to 18 h and 7 to 25 h, respectively. No hyperpressure was observed (porcine and human portal pressure 2-6 and 2-8 mm Hg; arterial pressure 10-65 and 20-65 mm Hg, respectively). No severe histological tissue injury was observed (Suzuki score ≤ 3 at the end of perfusion). Seven (70%) porcine livers and five (42%) human livers met the UK viability criteria. CONCLUSION: The customized circuit and system design enables smooth uninterrupted "cold-to-warm" perfusion not present in current commercial perfusion systems.

Cold-to-warm machine perfusion of the liver: a novel circuit for an uninterrupted combined perfusion protocol.

BACKGROUND: Ex-vivo perfusion of liver grafts is associated with promising results for the preservation of marginal grafts. Recent studies highlight the need for a combination of perfusion conditions, such as hypothermic followed by normothermic perfusion. While comprehensive machines dedicated to liver perfusion have been developed, these systems remain costly and poorly adaptable to perfusion condition switch, which requires a complete interruption of the perfusion process. Our team aimed at developing an adaptable and simple circuit for uninterrupted ex-vivo liver perfusion. METHODS: Together with specialized bioengineers, we developed a highly adaptable circuit that can fit on already pre-existing extracorporeal oxygenation machines routinely used in cardiovascular surgery. This circuit, owing to its reservoir, allows any type of perfusion conditions without interrupting the perfusion process. RESULTS: In a preliminary study, to assess the technical feasibility of liver perfusion using our circuit under different conditions, we performed 7 perfusions of discarded liver grafts. HOPE and DHOPE hypothermic perfusion could be performed, and a switch to normothermia was easily possible within seconds. From there, a dynamic perfusion sequence model was developed. CONCLUSION: This circuit may represent a simpler alternative or a new refinement to existing perfusion systems allowing uninterrupted combined perfusion protocols.

Survey: retrospective survey of monitoring/safety devices and incidents of cardiopulmonary bypass for cardiac surgery in France.

Several surveys showed that cardiopulmonary bypass (CPB) is associated with incidents that negatively affect outcome and suggested that improved monitoring and safety could be associated with a decreased rate of incidents. In 2004, the French "Haute Autorité de Santé" (an independent French government advisory agency) and the French College of Perfusion issued recommendations concerning safety and monitoring devices for CPB. The aims of this study were to investigate the difference between the recommendations and the clinical practice of CPB shortly after publication of the recommendations and compare the 2005 situation with the results of a previous survey performed in France and to investigate the rate of perfusion incidents and their outcome. A 62-item questionnaire was sent in January 2006 to all 66 centers performing cardiac surgery and CPB in France. The survey investigated the use of safety and monitoring devices as well as perfusion incidents for 2005. Fifty-seven centers (response rate, 86%) returned the questionnaire, totaling 34,496 CPB procedures. There was a wide difference between the recommendations and the reported use of safety and monitoring devices with no clinically relevant change from the previous French survey concerning 2001. An incident was reported for every 198 CPB procedures with death at a frequency of 1:4864 and permanent sequelae of 1:11,349, respectively (a permanent injury or death in 1:3220 procedures). The three most frequent perfusion incidents were adverse effects to protamine (1:1702), dissection at the arterial cannulation site (1:1792), and coagulation of the circuit (1:4864). In conclusion, this survey showed that an important effort must be made in France to implement into clinical practice the recommendations concerning CPB monitoring and safety devices. The analysis of CPB-related incidents suggest that, with the exception of protamine adverse effects, the majority of deaths and severe permanent injuries in this survey could probably be avoided by improved use of the monitoring and safety devices.