Evaluation of the Impact of Dexmedetomidine on Allograft Function Recovery and Survival Following Liver Transplantation: A Randomised Control Trial
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 330
- 试验地点
- 1
- 主要终点
- Incidence of early allograft dysfunction (EAD) following surgery
研究概览
简要总结
1.1. Background 1.1.1. Perioperative ischaemia/reperfusion (I/R) injury during liver transplantation is strongly associated with early allograft dysfunction, graft loss, and mortality.
1.1.2. Hepatic I/R injury also causes remote damage to other organs including the renal and pulmonary systems.
1.1.3. Dexmedetomidine, a selective α2-adrenoceptor agonist which is widely used as an adjuvant to general anaesthesia, has been widely shown in preclinical studies to provide organoprotection by ameliorating the effects of I/R injury in a range of tissues (including the liver). However, prospective clinical evidence of any potential benefits in improving outcomes in liver transplantation is lacking.
1.2. Objectives 1.2.1. To investigate the hypothesis that perioperative treatment with dexmedetomidine reduces the incidence of early allograft dysfunction and primary graft non-function in deceased donor liver transplantation.
1.2.2. The impact of dexmedetomidine on postoperative renal and pulmonary function will also be examined.
1.3. Study Design This is a prospective, single-centre, randomised, parallel-group study.
1.4. Setting Departments of Anesthesiology, Renji Hosptial, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
1.5. Patients 200 patients (18-65 years) scheduled to undergo liver transplantation under general anaesthesia.
1.6 Intervention 1.6.1. For the patients in the treatment group, a loading dose of dexmedetomidine will be given after induction of anaesthesia (1μg/kg over 10 min) followed by a continuous infusion (0.5μg/kg /h) until the end of surgery.
1.6.2. For patients in the placebo group, an equal volume loading dose of 0.9% saline will be given after the induction of anaesthesia followed by an equal volume continuous infusion until the end of surgery.
1.6.3. All other supplements, e.g. opioids, sedatives and muscle relaxant, will be identical in the both arms and administered according to routine clinical practice.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years
- •Scheduled to undergo allogenic liver transplant(DCD/DBD) surgery under general anaesthesia
- •Patients should meet the UCSF criteria
- •Agree to participate and give written informed consent
排除标准
- •Severe renal dysfunction (undergoing renal replacement therapy before surgery)
- •Severe pulmonary dysfunction (including pneumonia, atelectasis, pleural effusion, acute lung injury or ARDS)
- •Severe circulatory instability (severe coronary artery disease, unstable angina, left ventricular ejection fraction < 30%, sick sinus syndrome, severe sinus bradycardia [< 50 bpm], second-degree or greater atrioventricular block)
- •Known allergy or intolerance to trial medication
- •Refusal to participate in the study
- •Participation in other clinical trials within 30 days prior to randomisation.
- •Retransplantation
- •Multiple organ transplantation
- •Other reasons that are considered unsuitable for study participation by the responsible surgeon or anaesthetist (reasons must be documented in the case report form [CRF])
研究组 & 干预措施
Dexmedetomidine treatment group
Anaesthesia will be maintained with sevoflurane inhalation, of which the concentration will be adjusted to maintain the BIS value between 40 and 60. Muscle relaxation will be maintained with rocuronium or cisatracurium. Analgesia will be maintained with remifentanil (administered via continuous infusion), sufentanil (administered via continuous infusion or intermittent injection), or fentanyl (administered via intermittent injection). In addition to this, patients will receive an initial loading dose of dexmedetomidine of 1μg/kg over 10 min after the induction of anaesthesia followed by a continuous infusion of 0.5μg/kg/h until the end of surgery.
干预措施: Dexmedetomidine (Drug)
Control group
Anaesthesia will be maintained with sevoflurane inhalation, of which the concentration will be adjusted to maintain the BIS value between 40 and 60. Muscle relaxation will be maintained with rocuronium or cisatracurium. Analgesia will be maintained with remifentanil (administered via continuous infusion), sufentanil (administered via continuous infusion or intermittent injection), or fentanyl (administered via intermittent injection). In addition to this, patients will receive an equal volume initial loading dose of 0.9% saline over 10 min after the induction of anaesthesia followed by an equal volume continuous infusion until the end of surgery.
干预措施: Saline (Drug)
结局指标
主要结局
Incidence of early allograft dysfunction (EAD) following surgery
时间窗: 7 days
Defined according to Olthoff's criteria published in 2010: (1) bilirubin ≥ 10mg/dL on day 7; or (2) INR \> 1.6 on day 7; or (3) AST/ ALT \> 2000IU/L within first 7 days.
次要结局
- Incidence of postoperative acute kidney injury (AKI) during the postoperative day 1-7(7 days)
- Incidence of acute respiratory distress syndrome (ARDS) during the postoperative day 1-7(7 days)
- Incidence of graft failure and retransplantation rate during 3 year follow up period.(3 years)
- All cause mortality in the 3 year follow-up period.(3 years)
- Incidence of primary graft non-function (PNF)(30 days)