Cardiac output Optimisation following Liver Transplant (COLT) trial: study protocol for a feasibility randomised controlled trial.

ABSTRACT

BACKGROUND: Patients with liver cirrhosis undergoing liver transplantation have a hyperdynamic circulation which persists into the early postoperative period making accurate assessment of fluid requirements challenging. Goal-directed fluid therapy (GDFT) has been shown to reduce morbidity and mortality in a number of surgery settings. The impact of GDFT in patients undergoing liver transplantation is unknown. A feasibility trial was designed to determine patient and clinician support for recruitment into a randomised controlled trial of GDFT following liver transplantation, adherence to a GDFT protocol, participant withdrawal, and to determine appropriate endpoints for a subsequent larger trial to evaluate the efficacy of GDFT in patients undergoing liver transplantation. METHODS: The Cardiac output Optimisation following Liver Transplant (COLT) trial is designed as a prospective, single-centre, randomised controlled study to assess the feasibility and safety of GDFT in liver transplantation for patients with cirrhosis. Consenting adults (aged between 18 and 80 years) with biopsy-proven liver cirrhosis who have been selected to undergo a first liver transplantation will be included in the trial and randomised into GDFT or standard care starting immediately after surgery and continuing for the first 12 h thereafter. Both groups will have cardiac output and stroke volume monitored using the FloTrac (EV1000) device. The intervention will consist of a protocolised GDFT approach to patient management, using stroke volume optimisation. The control group will receive standard care, without stroke volume and cardiac output measurement. After 12 h the patient's fluid management will revert to standard of care. The primary endpoint of this study is feasibility. Secondary endpoints will include a safety assessment of the intervention, graft and patient survival, liver function, postoperative complications graded by Clavien-Dindo criteria, length of intensive care and hospital stay and quality of life across the intervention and control groups. DISCUSSION: There is a growing body of evidence that the use of perioperative GDFT in surgical patients can improve outcomes; however, signals of harm have also been detected. Patients with liver cirrhosis undergoing liver transplantation have markedly different cardiovascular physiology than general surgical patients. If GDFT is proven to be feasible and safe in this patient group, then a multicentre trial to demonstrate efficacy and cost-effectiveness will be required. TRIAL REGISTRATION International Standard Randomised Controlled Trial Registry, ID ISRCTN10329248. Registered on 4 April 2016.