Restrictive fluid management in liver transplantation: the REFIL randomized controlled trial
BACKGROUND
Liver transplant recipients suffer from many postoperative complications and few perioperative interventions have been shown to decrease them. The effects of intraoperative fluid management on postoperative complications has been well studied in different surgical populations, but the applicability of this data to liver transplant recipients is limited. Our systematic review suggested that an intraoperative restrictive fluid administration might have a protective effect on intraoperative bleeding and postoperative complications, but the quality of evidence was insufficient to draw any definitive conclusion. Since equipoise is unresolved on the best intraoperative fluid management strategy to use in this population, we will first conduct a pilot multicenter randomized controlled trial (RCT) comparing an intraoperative restrictive fluid management strategy to a liberal one in adult liver transplantation.
OBJECTIVES
The primary objective of this pilot study is to evaluate the feasibility of a future definitive intraopeative fluid management RCT in liver transplantation among Canadian liver transplantation centers. The secondary objective is to start gather blinded data for a future efficacy trial by using this pilot study as a vanguard phase of such a future trial.
METHODS
We will compare a restrictive fluid management strategy to a liberal one applied during the dissection and the anhepatic phases of a liver transplantation. 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 primary feasibility outcome will be a recruitment rates ≥ 4 patients/month over a 16-month period and our secondary feasibility outcomes will be a protocol adherence greater than 80% and a difference in exposure between groups of at least 1000 ml of average total volume received (crystalloids and colloids combined). Our tertiary efficacy outcomes will be a composite of death, retransplantation or any Dindo-Clavien grade III or more complication up to 30 days. We will measure other outcomes such as perioperative blood loss and transfusions, graft dysfunction, biliary complications, acute kidney injury, pulmonary complications, infectious complications, persistent organ dysfunction, hospital length of stay, survival up to one year and quality of life. We will keep results of our efficacy outcomes concealed to rollover included patients in this pilot phase within the future efficacy trial, pending such a trial is feasible. We plan to include 64 patients in this pilot RCT, a sample powered to provide a 95% confidence interval of 70-90% for our adherence outcome and to measure a 1000 mL difference between groups.
IMPACT
This trial will be conducted over 16 months in three Canadian centers to validate the feasibility of a perioperative multicenter RCT. This study will build a canadian research infrastructure to conduct of a well-powered multicenter efficacy trial that will answer the question regarding the best intraoperative fluid management to use in liver transplantation. We have assembled a multidisciplinary team of investigators with complementary clinical and research skills, notably in the conduct of multicenter trials. This trial is endorsed by the Canadian PACT (Perioperative Anesthesia Clinical Trail group) and the CDTRP (Canadian Donation and Transplantation Research Program). This pilot trial will help us move forward to conduct a large-scale efficacy trial to answer this important research question.
