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

Abstract

BackgroundPatients 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.MethodsThe 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.DiscussionThere 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 registrationInternational Standard Randomised Controlled Trial Registry, ID: ISRCTN10329248. Registered on 4 April 2016.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2488-8) contains supplementary material, which is available to authorized users.

Urinary Neutrophil Gelatinase Associated Lipocalins (NGALs) predict acute kidney injury post liver transplant

“…27 Its role in reducing the incidence of AKI post liver transplant remains to be elucidated but is the subject of a current trial. 28 A randomized controlled trial of goal directed therapy in patients with raised NGAL levels would be an attractive method of identifying whether GDT post transplant reduces AKI in patients with evidence of renal injury. However biomarker validation would be required before this trial design could be justified.…”

Fluid balance in pediatric postoperative liver transplant recipients

“…Growing evidence of the deleterious effects of positive FB in critically ill children, including the findings of this study, suggest that close monitoring of postoperative FB is important and that intervention in postoperative fluid management with attention to potential associations with postoperative complications should be evaluated 16 . A single‐center feasibility randomized controlled trial currently ongoing is investigating goal‐directed fluid therapy in adult LT recipients using stroke volume optimization 30 . Goal‐directed fluid therapy and advanced coagulation monitoring tools such as thromboelastography may allow for precise management of FB, hemodynamics, and hypercoagulable state in pediatric LT recipients.…”

The cardiac output optimisation following liver transplant (COLT) trial: a feasibility randomised controlled trial

“…The protocol for this study has been published previously. 15 We conducted an RCT of GDFT versus standard IV fluid management in a single centre in the United Kingdom to assess the feasibility of conducting a postoperative fluid optimisation trial in patients who have undergone liver transplantation. Secondarily, we compared the intervention and standard care (SC) groups to assess the safety profile of GDFT and to collect information on clinical outcomes and quality of life, evaluated potential primary outcomes for a subsequent trial to assess the efficacy of GDFT in liver transplantation and examined the cost effectiveness of the intervention.…”

“…The median ICU length of stay was 3.5 (3)(4)(5)(6)(7)(8)(9)(10) days in the GDFT group and 3.0 (2-8) days in the SC group (p = 0.673); median hospital length of stay was 26.0 (18-41) days for the GDFT group and 23.0 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) days for the SC group (p = 0.473). Five patients had at least one readmission to ICU from GDFT (16.7%) group and three (10%) from the SC group, but this was not statistically significant (difference in proportion: 6.7% (95%: −10.5 to 23.8)).…”

“…A predetermined recruitment of greater than 40% of patients fulfilling the criteria for this study was deemed to indicate success. A number of predetermined secondary outcomes were also measured (Table 2), 15 including postoperative complications. 16 Quality of life (QoL) was assessed by asking participants to complete an EQ-5D-5L assessment immediately prior to surgery, at discharge from hospital, and 90 and 180 days after surgery.…”