Restrictive fluid management in liver transplantation: the REFIL randomized controlled trial
BACKGROUND
Liver transplant recipients often suffer from important postoperative complications with few perioperative interventions decreasing their incidence. The effects of different intraoperative hemodynamic management strategies have been well studied in different surgical populations, but the applicability of this data to liver transplant recipients is limited. Observational data support the use of an intraoperative phlebotomy to reduce splanchnic blood volume, blood loss and transfusions and that targeting a lower fluid balance may improve outcomes. Our systematic review suggested, based on low or very low quality of evidence, that an intraoperative restrictive fluid management strategy might reduce blood loss and the risk of postoperative complications. However, clinical practice is still variable, and equipoise is unresolved on the best intraoperative hemodynamic management strategy to implement in this population. Our pilot data shows that a multicenter trial on intraoperative hemodynamic management is feasible in this population.
OBJECTIVES
We propose to conduct a multicenter efficacy randomized controlled trial comparing an intraoperative low splanchnic blood volume restrictive fluid management strategy to a liberal one in adult liver transplantation. Our primary objective is to estimate the effect of this intervention on the incidence of severe postoperative complications. Our secondary objectives are to estimate such effect on other outcomes, including transfusions requirements, quality of recovery, and biomarkers, as well as its costeffectiveness.
METHODS
We will compare a low splanchnic blood volume restrictive fluid management strategy to a liberal one applied during liver transplantation up to graft reperfusion. Our intervention (restrictive fluid management) will include a phlebotomy performed before incision combined with a restrictive use of fluid to only compensate blood loss and treat significant hemodynamic instability. Our comparison group (liberal fluid management) will not receive a phlebotomy and will receive a liberal use of fluids. Our primary efficacy
outcome will be the incidence of any severe complication defined as any Dindo-Clavien grade III or more complication up to hospital discharge. We will measure other outcomes such as perioperative blood loss and transfusions, acute kidney injury, graft, biliary, pulmonary, infectious, cardiovascular and thromboembolic complications, persistent organ dysfunction, 7-day quality of recovery, survival up to one year and 6-month and 12-month quality of life. The allocated intervention will be concealed to research staff. The primary outcome, graft complications and quality of life will be centrally adjudicated. We plan to include 866 patients over five years in 7 Canadian centers and 4 French centers.
SCOPE
This study will foster an existing research infrastructure that was built for our international multicenter cohort study and our pilot multicenter Canadian trial to conduct a well-powered multicenter efficacy trial answering the question regarding the best intraoperative hemodynamic management strategy in liver transplantation. We have assembled a multidisciplinary team of investigators with complementary clinical and research skills to conduct this study, that is supported by recognized research networks. The results of this study may lead to the implementation of an intraoperative hemodynamic management strategy that improves patients' outcomes.
