Froghi Farid, Koti Rahul, Gurusamy Kurinchi, Mallett Susan, Thorburn Douglas, Selves Linda, James Sarah, Singh Jeshika, Pinto Manuel, Eastgate Christine, McNeil Margaret, Filipe Helder, Jichi Fatima, Schofield Nick, Martin Daniel, Davidson Brian
Division of Surgery and Interventional Science, University College London, London, UK.
Critical Care Unit, Royal Free Hospital, London, NW3 2QG, UK.
Trials. 2018 Mar 7;19(1):170. doi: 10.1186/s13063-018-2488-8.
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.
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.
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.
International Standard Randomised Controlled Trial Registry, ID: ISRCTN10329248. Registered on 4 April 2016.
接受肝移植的肝硬化患者存在高动力循环，这种情况会持续到术后早期，使得准确评估液体需求量具有挑战性。目标导向液体治疗（GDFT）已被证明可降低多种手术情况下的发病率和死亡率。GDFT对肝移植患者的影响尚不清楚。一项可行性试验旨在确定患者和临床医生对招募入肝移植后GDFT随机对照试验的支持度、对GDFT方案的依从性、参与者退出情况，并为后续更大规模试验确定合适的终点指标，以评估GDFT对肝移植患者的疗效。
肝移植后心输出量优化（COLT）试验设计为一项前瞻性、单中心、随机对照研究，以评估GDFT在肝硬化患者肝移植中的可行性和安全性。经活检证实为肝硬化且已被选定接受首次肝移植的同意参与的成年人（年龄在18至80岁之间）将被纳入试验，并在术后立即随机分为GDFT组或标准治疗组，此后持续12小时。两组均使用FloTrac（EV1000）设备监测心输出量和每搏输出量。干预措施将包括采用每搏输出量优化的标准化GDFT方法进行患者管理。对照组将接受标准治疗，不测量每搏输出量和心输出量。12小时后，患者的液体管理将恢复为标准治疗。本研究的主要终点是可行性。次要终点将包括对干预措施的安全性评估、移植物和患者生存率、肝功能、根据Clavien-Dindo标准分级的术后并发症、重症监护和住院时间以及干预组和对照组的生活质量。
越来越多的证据表明，围手术期对手术患者使用GDFT可改善预后；然而，也发现了有害信号。接受肝移植的肝硬化患者的心血管生理与普通外科患者明显不同。如果GDFT在该患者群体中被证明是可行和安全的，那么将需要进行一项多中心试验来证明其疗效和成本效益。
国际标准随机对照试验注册库，编号：ISRCTN10329248。于2016年4月4日注册。
