Devlin John W, Sieber Frederick, Akeju Oluwaseun, Khan Babar A, MacLullich Alasdair M J, Marcantonio Edward R, Oh Esther S, Agar Meera R, Avelino-Silva Thiago J, Berger Miles, Burry Lisa, Colantuoni Elizabeth A, Evered Lis A, Girard Timothy D, Han Jin H, Hosie Annmarie, Hughes Christopher, Jones Richard N, Pandharipande Pratik P, Subramanian Balachundhar, Travison Thomas G, van den Boogaard Mark, Inouye Sharon K
Department of Pharmacy and Health Systems Sciences, Bouve College of Health Sciences, Northeastern University, Boston, MA.
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA.
Crit Care Med. 2025 Jan 1;53(1):e15-e28. doi: 10.1097/CCM.0000000000006514. Epub 2024 Nov 22.
To summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.
A 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).
To provide background and context, a review of delirium treatment randomized controlled trials (RCTs) published between 2003 and 2023 was conducted and evidence gaps were identified. The four panels addressed the identified subtopics. For each subtopic, research challenges were identified and recommendations to address each were proposed through virtual discussion before a live, full-day, and in-person conference. General agreement was reached for each proposed recommendation across the entire working group via moderated conference discussion. Recommendations were synthesized across panels and iteratively discussed through rounds of virtual meetings and draft reviews.
We identified key evidence gaps through a systematic literature review, yielding 43 RCTs of delirium treatments. From this review, eight unique challenges for delirium treatment trials were identified, and recommendations to address each were made based on panel input. The recommendations start with design of interventions that consider the multifactorial nature of delirium, include both pharmacological and nonpharmacologic approaches, and target pathophysiologic pathways where possible. Selecting appropriate at-risk patients with moderate vulnerability to delirium may maximize effectiveness. Targeting patients with at least moderate delirium severity and duration will include those most likely to experience adverse outcomes. Delirium severity should be the primary outcome of choice; measurement of short- and long-term clinical outcomes will maximize clinical relevance. Finally, plans for handling informative censoring and missing data are key.
By addressing key delirium treatment challenges and research gaps, our recommendations may serve as a roadmap for advancing delirium treatment research in older adults.
总结谵妄治疗试验文献，识别谵妄治疗试验中的独特挑战，并制定针对老年人应对每项挑战的建议。
召集了一个由39名成员组成的跨专业国际专家工作组，成员包括临床医生（内科医生、护士和药剂师）和非临床医生（生物统计学家、流行病学家和试验方法学家）。组建了四个专家小组来探讨关键子主题（药物/非药物治疗、方法学挑战和新颖研究设计）。
为提供背景和情境，对2003年至2023年间发表的谵妄治疗随机对照试验（RCT）进行了综述，并确定了证据空白。四个小组讨论了确定的子主题。对于每个子主题，识别了研究挑战，并通过在现场全天面对面会议之前的虚拟讨论提出了应对每项挑战的建议。通过主持会议讨论，在整个工作组中就每项提议的建议达成了总体共识。跨小组综合了建议，并通过多轮虚拟会议和草案评审进行了反复讨论。
通过系统的文献综述，我们确定了关键证据空白，产生了43项谵妄治疗的RCT。从这次综述中，识别出了谵妄治疗试验的八个独特挑战，并根据小组意见提出了应对每项挑战的建议。这些建议首先从设计干预措施开始，要考虑到谵妄的多因素性质，包括药物和非药物方法，并尽可能针对病理生理途径。选择对谵妄有中度易感性的合适高危患者可能会使效果最大化。针对谵妄严重程度和持续时间至少为中度的患者，将包括那些最有可能经历不良后果的患者。谵妄严重程度应是首选的主要结局；对短期和长期临床结局的测量将使临床相关性最大化。最后，处理信息性删失和缺失数据的计划很关键。
通过应对谵妄治疗的关键挑战和研究空白，我们的建议可作为推进老年人谵妄治疗研究的路线图。
