Objectives

Postoperative delirium, associated with negative consequences including longer hospital stays and worse cognitive and physical outcomes, is frequently accompanied by sleep-wake disturbance. Our objective was to evaluate the efficacy and short-term safety of ramelteon, a melatonin receptor agonist, for the prevention of postoperative delirium in older patients undergoing orthopedic surgery.

Design

A quadruple-masked randomized placebo-controlled trial (Clinical Trials.gov NCT02324153) conducted from March 2017 to June 2019.

Setting

Tertiary academic medical center.

Participants

Patients aged 65 years or older, undergoing elective primary or revision hip or knee replacement.

Intervention

Ramelteon (8 mg) or placebo

Measurements

Eighty participants were randomized to an oral gel cap of ramelteon or placebo for 3 consecutive nights starting the night before surgery. Trained research staff conducted delirium assessments for 3 consecutive days starting on postoperative day (POD) 0, after recovery from anesthesia, and on to POD2. A delirium diagnosis was based upon DSM-5 criteria determined by expert panel consensus.

Results

Of 80 participants, five withdrew consent (one placebo, four ramelteon) and four were excluded (four ramelteon) after randomization. Delirium incidence during the 2 days following surgery was 7% (5 of 71) with no difference between the ramelteon versus placebo: 9% (3 of 33) and 5% (2 of 38), respectively. The adjusted odds ratio for postoperative delirium as a function of assignment to the ramelteon treatment arm was 1.28 (95% confidence interval: 0.21–7.93; z-value 0.27; p-value = 0.79). Adverse events were similar between the two groups.

Conclusion

In older patients undergoing elective primary or revision hip or knee replacement, ramelteon was not efficacious in preventing postoperative delirium.

中文翻译：

---

雷美替胺对预防接受骨科手术的老年患者术后谵妄的影响：RECOVER 随机对照试验。

目标

术后谵妄与负面后果相关，包括更长的住院时间以及更差的认知和身体结果，通常伴有睡眠-觉醒障碍。我们的目的是评估雷美替胺（一种褪黑激素受体激动剂）预防接受骨科手术的老年患者术后谵妄的疗效和短期安全性。

设计

2017 年 3 月至 2019 年 6 月进行的一项四重盲随机安慰剂对照试验 (Clinical Trials.gov NCT02324153)。

环境

三级学术医疗中心。

参加者

年龄 65 岁或以上、接受选择性初次或翻修髋关节或膝关节置换术的患者。

干涉

Ramelteon（8 毫克）或安慰剂

测量

从手术前一晚开始，80 名参与者被随机分配服用雷美替胺口服凝胶帽或安慰剂，连续 3 晚服用。训练有素的研究人员从术后第 0 天（POD）麻醉恢复后开始连续 3 天进行谵妄评估，一直到 POD2。谵妄诊断基于专家组共识确定的 DSM-5 标准。

结果

在 80 名参与者中，有 5 名受试者撤回同意（一名安慰剂，四名雷美替胺），四名受试者在随机分组后被排除（四名雷美替胺）。手术后 2 天内谵妄发生率为 7%（71 人中的 5 人），雷美替胺与安慰剂之间没有差异：分别为 9%（33 人中的 3 人）和 5%（38 人中的 2 人）。术后谵妄的调整比值比与雷美替胺治疗组的分配关系为 1.28（95% 置信区间：0.21-7.93；z 值 0.27；p 值 = 0.79）。两组之间的不良事件相似。

结论

在接受选择性初次或翻修髋关节或膝关节置换术的老年患者中，雷美替胺不能有效预防术后谵妄。