Proportional Sedation for Persistent Agitated Delirium in Palliative Care: A Randomized Clinical Trial.

Background

To compare the effect of scheduled haloperidol, lorazepam, haloperidol plus lorazepam, and placebo on patients with advanced cancer and delirium and experiencing restlessness and/or agitation in the palliative care setting.

本研究旨在比较计划性使用氟哌啶醇、劳拉西泮、氟哌啶醇加劳拉西泮以及安慰剂对晚期癌症患者在姑息治疗环境中出现谵妄和烦躁/焦虑症状的影响。

DESIGN, SETTINGS, AND PARTICIPANTS: This multicenter randomized clinical trial was conducted at 3 acute palliative care units in Taiwan and the US with patients with advanced cancer experiencing persistent restlessness and/or agitation despite nonpharmacologic therapies and standard-dose haloperidol.

设计、设置和参与者：这项多中心随机临床试验在台湾和美国的3个急性姑息治疗单位进行，对象为尽管接受了非药物治疗和标准剂量的氟哌啶醇治疗，但仍然持续出现不安和/或烦躁的晚期癌症患者。

Among 245 eligible patients, 111 were enrolled, and 75 received blinded treatments.

在245名符合条件的患者中，有111名被纳入研究，其中75名接受了盲法治疗。

Participants were randomized in a 1:1:1:1 ratio (stratified by site and Richmond Agitation-Sedation Scale [RASS] score).

参与者按1:1:1:1的比例随机分组（按地点和Richmond激动-镇静评分[RASS]进行分层）。

The study period was from July 16, 2019, to June 8, 2023, with a 30-day follow-up after medication administration.

研究期间为2019年7月16日至2023年6月8日，药物给药后有30天的随访期。

Data analysis was performed from October 10, 2023, to April 11, 2025.

数据分析从2023年10月10日进行至2025年4月11日。

Methods

Scheduled intravenous haloperidol, lorazepam, haloperidol plus lorazepam, or placebo every 4 hours until discharge, death, or withdrawal from study.

计划每4小时通过静脉给予氟哌啶醇、劳拉西泮、氟哌啶醇加劳拉西泮或安慰剂，直至出院、死亡或退出研究。

Medications in all 4 groups had identical volume and appearance.

所有4组药物的体积和外观完全相同。

main_outcomes_and_measures

Change in RASS scores during the first 24 hours.

在最初的24小时内RASS评分的变化。

Secondary outcomes included the use of rescue neuroleptics or benzodiazepines for breakthrough restlessness or agitation during the first 24 hours, delirium severity, perceived patient comfort, and adverse events.

次要结果包括在前24小时内因突破性不安或激动使用急救抗精神病药物或苯二氮卓类药物、谵妄严重程度、患者舒适度感知以及不良事件。

Results

The primary outcome was assessed in 72 patients (mean [SD] age, 64 [12] years, 42 male [58%]) with a median (IQR) MDAS score of 24 (18-29).

主要结果在72名患者中进行了评估（平均[标准差]年龄，64[12]岁，42名男性[58%]），中位数（四分位数间距）MDAS评分为24（18-29）。

The lorazepam group had significantly lower RASS scores than the haloperidol group (mean difference, -2.1; 95% CI, -3.4 to -0.9; P < .001) and the combination group had significantly lower RASS scores than the haloperidol group (-2.0; 95% CI, -3.2 to -0.8; P = .002); however, there was no difference observed between haloperidol and placebo groups (-0.5; 95% CI, -1.7 to 0.7; P = .42) nor between the combination and lorazepam groups (0.2; 95% CI, -1.1 to 1.4; P = .79).

劳拉西泮组的RASS评分显著低于氟哌啶醇组（平均差异，-2.1；95%置信区间，-3.4至-0.9；P < .001），联合用药组的RASS评分也显著低于氟哌啶醇组（-2.0；95%置信区间，-3.2至-0.8；P = .002）；然而，在氟哌啶醇组和安慰剂组之间（-0.5；95%置信区间，-1.7至0.7；P = .42）以及联合用药组和劳拉西泮组之间（0.2；95%置信区间，-1.1至1.4；P = .79）未观察到差异。

The combination and lorazepam groups required fewer rescue medications for breakthrough restlessness or agitation compared to the haloperidol and placebo groups (32%, 37%, 56%, 83%, respectively; P = .006).

联合用药组和劳拉西泮组在突破性不安或激动时需要较少的急救药物，与氟哌啶醇组和安慰剂组相比（分别为32%，37%，56%，83%；P = .006）。

Adverse events or survival did not differ between groups.

不良事件或总生存率在各组之间没有差异。

conclusions_and_relevance

The results of this randomized clinical trial indicate that proactive use of scheduled sedatives, particularly lorazepam-based regimens, may reduce persistent restlessness and/or agitation in patients with advanced cancer and delirium in the palliative care setting.

这项随机临床试验的结果表明，积极使用计划性的镇静剂，特别是以劳拉西泮为基础的方案，可能减少晚期癌症患者和姑息治疗环境中出现持续性不安和/或躁动。

trial_registration

Clinicaltrials.gov Identifier: NCT03743649.

临床试验注册号：NCT03743649。