DAS-OLT 试验的研究设计：一项随机对照试验，旨在评估右美托咪定对肝移植后早期移植物功能障碍的影响。
Study design of the DAS-OLT trial: a randomized controlled trial to evaluate the impact of dexmedetomidine on early allograft dysfunction following liver transplantation.
机构信息
Department of Anesthesiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160 Pujian Road, Shanghai, 200127, China.
Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
出版信息
Trials. 2020 Jun 26;21(1):582. doi: 10.1186/s13063-020-04497-7.
BACKGROUND
Perioperative ischemia/reperfusion (I/R) injury during liver transplantation is strongly associated with early allograft dysfunction (EAD), graft loss, and mortality. Hepatic I/R injury also causes remote damage to other organs including the renal and pulmonary systems. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist which is used as an adjuvant to general anesthesia, has been shown in preclinical studies to provide organ protection 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. This study aimed to verify the hypothesis that the application of dexmedetomidine during the perioperative period of liver transplantation can reduce the incidence of EAD and primary graft non-function (PNF). At the same time, the effects of dexmedetomidine application on perioperative renal function and lung function were studied.
METHODS
This is a prospective, single-center, randomized, parallel-group study. Two hundred participants (18-65 years) scheduled to undergo liver transplantation under general anesthesia will be included in this study. For participants in the treatment group, a loading dose of DEX will be given after induction of anesthesia (1 μg/kg over 10 min) followed by a continuous infusion (0.5 μg/kg /h) until the end of surgery. For participants in the placebo group, an equal volume loading dose of 0.9% saline will be given after the induction of anesthesia followed by an equal volume continuous infusion until the end of surgery. All other supplements, e.g., opioids, sedatives, and muscle relaxant, will be identical in both arms and administered according to routine clinical practice.
DISCUSSION
The present trial will examine whether DEX confers organoprotective effects in the liver, in terms of reducing the incidence of EAD and PNF in orthotopic liver transplantation recipients.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03770130. Registered on 10 December 2018. https://clinicaltrials.gov/ct2/show/NCT03770130.
背景
肝移植过程中的围手术期缺血/再灌注（I/R）损伤与早期移植物功能障碍（EAD）、移植物丢失和死亡率密切相关。肝 I/R 损伤还会导致其他器官（包括肾脏和肺部系统）的远程损伤。右美托咪定（DEX）是一种选择性 α2-肾上腺素能受体激动剂，用作全身麻醉的辅助剂，已在临床前研究中显示，通过改善多种组织（包括肝脏）的 I/R 损伤的作用来提供器官保护。然而，缺乏关于在肝移植中改善结果方面任何潜在益处的前瞻性临床证据。本研究旨在验证以下假设：在肝移植围手术期应用右美托咪定可以降低 EAD 和原发性移植物功能障碍（PNF）的发生率。同时，研究了右美托咪定应用对围手术期肾功能和肺功能的影响。
方法
这是一项前瞻性、单中心、随机、平行组研究。将纳入 200 名接受全身麻醉下肝移植的参与者（18-65 岁）参与本研究。治疗组的参与者在诱导麻醉后给予右美托咪定负荷剂量（1μg/kg 持续 10 分钟），然后持续输注（0.5μg/kg/h）至手术结束。在安慰剂组中，参与者在诱导麻醉后给予等量的 0.9%生理盐水负荷剂量，然后给予等量的持续输注直至手术结束。在两个组中，其他补充剂，如阿片类药物、镇静剂和肌肉松弛剂，将完全相同，并根据常规临床实践进行给药。
讨论
本试验将研究 DEX 是否在肝脏中具有器官保护作用，从而降低原位肝移植受者 EAD 和 PNF 的发生率。
试验注册
ClinicalTrials.gov NCT03770130。于 2018 年 12 月 10 日注册。https://clinicaltrials.gov/ct2/show/NCT03770130。
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