Shelton Kenneth T, Qu Jason, Bilotta Federico, Brown Emery N, Cudemus Gaston, D'Alessandro David A, Deng Hao, DiBiasio Alan, Gitlin Jacob A, Hahm Eunice Y, Hobbs Lauren E, Houle Timothy T, Ibala Reine, Loggia Marco L, Pavone Kara J, Shaefi Shahzad, Tolis George, Westover M Brandon, Akeju Oluwaseun
Department of Anesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Department of Anaesthesia and Critical Care Medicine, Sapienza University of Rome, Rome, Italy.
BMJ Open. 2018 Apr 20;8(4):e020316. doi: 10.1136/bmjopen-2017-020316.
Delirium, which is prevalent in postcardiac surgical patients, is an acute brain dysfunction characterised by disturbances in attention, awareness and cognition not explained by a pre-existing neurocognitive disorder. The pathophysiology of delirium remains poorly understood. However, basic science and clinical studies suggest that sleep disturbance may be a modifiable risk factor for the development of delirium. Dexmedetomidine is a α-2A adrenergic receptor agonist medication that patterns the activity of various arousal nuclei similar to sleep. A single night-time loading dose of dexmedetomidine promotes non-rapid eye movement sleep stages N2 and N3 sleep. This trial hypothesises dexmedetomidine-induced sleep as pre-emptive therapy for postoperative delirium.
The MINDDS (Minimizing ICU Neurological Dysfunction with Dexmedetomidine-induced Sleep) trial is a 370-patient block-randomised, placebo-controlled, double-blinded, single-site, parallel-arm superiority trial. Patients over 60 years old, undergoing cardiac surgery with planned cardiopulmonary bypass, will be randomised to receive a sleep-inducing dose of dexmedetomidine or placebo. The primary outcome is the incidence of delirium on postoperative day 1, assessed with the Confusion Assessment Method by staff blinded to the treatment assignment. To ensure that the study is appropriately powered for the primary outcome measure, patients will be recruited and randomised into the study until 370 patients receive the study intervention on postoperative day 0. Secondary outcomes will be evaluated by in-person assessments and medical record review for in-hospital end points, and by telephone interview for 30-day, 90-day and 180-day end points. All trial outcomes will be evaluated using an intention-to-treat analysis plan. Hypothesis testing will be performed using a two-sided significance level (type I error) of α=0.05. Sensitivity analyses using the actual treatment received will be performed and compared with the intention-to-treat analysis results. Additional sensitivity analyses will assess the potential impact of missing data due to loss of follow-up.
The Partners Human Research Committee approved the MINDDS trial. Recruitment began in March 2017. Dissemination plans include presentations at scientific conferences, scientific publications and popular media.
NCT02856594.
谵妄在心脏外科手术后患者中很常见，是一种急性脑功能障碍，其特征为注意力、意识和认知方面的紊乱，且不能用既往存在的神经认知障碍来解释。谵妄的病理生理学仍知之甚少。然而，基础科学和临床研究表明，睡眠障碍可能是谵妄发生的一个可改变的危险因素。右美托咪定是一种α-2A肾上腺素能受体激动剂药物，其作用模式类似于睡眠，可调节各种觉醒核团的活动。单次夜间负荷剂量的右美托咪定可促进非快速眼动睡眠的N2和N3期睡眠。本试验假设右美托咪定诱导的睡眠可作为术后谵妄的预防性治疗方法。
MINDDS（右美托咪定诱导睡眠使重症监护病房神经功能障碍最小化）试验是一项纳入370例患者的区组随机、安慰剂对照、双盲、单中心、平行组优效性试验。年龄超过60岁、计划进行体外循环心脏手术的患者将被随机分组，分别接受诱导睡眠剂量的右美托咪定或安慰剂。主要结局是术后第1天谵妄的发生率，由对治疗分配不知情的工作人员采用意识模糊评估法进行评估。为确保该研究有足够的检验效能用于主要结局指标，将持续招募患者并随机分组进入研究，直至370例患者在术后第0天接受研究干预。次要结局将通过现场评估和病历审查来评估住院终点，并通过电话访谈评估30天、90天和180天的终点。所有试验结局将使用意向性分析计划进行评估。假设检验将采用双侧显著性水平（I型错误）α=0.05。将进行使用实际接受治疗情况的敏感性分析，并与意向性分析结果进行比较。额外的敏感性分析将评估因失访导致的缺失数据的潜在影响。
合作伙伴人类研究委员会批准了MINDDS试验。招募工作于2017年3月开始。传播计划包括在科学会议上发表演讲、发表科学论文以及通过大众媒体进行传播。
NCT02856594。
