Prophylactic minocycline for delirium in critically ill patients: a randomized controlled trial

IF 9.5 1区 医学 Q1 CRITICAL CARE MEDICINE Chest Pub Date : 2023-12-01 DOI:10.1016/j.chest.2023.11.041
Felipe Dal-Pizzol, André Coelho, Carla S. Simon, Monique Michels, Emily Corneo, Aline Jeremias, Danusa Damásio, Cristiane Ritter
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Abstract

Background

Delirium is a potentially severe form of acute encephalopathy. Minocycline has neuroprotective effects in animal models of neurological diseases; however, data from human studies remain scarce.

Research Question

Does the neuroprotective effect of minocycline prevent delirium occurrence in critical ill patients?

Study design and Methods

This study was a randomized, placebo-controlled, double-blind trial conducted in four Intensive Care Units (ICUs). Patients aged 18 years or older were eligible and randomized to receive minocycline (100 mg twice a day) or placebo. The primary outcome was delirium incidence within 28 days or before ICU discharge. Secondary outcomes included days in delirium during ICU stay, delirium/coma free days, length of mechanical ventilation, ICU length of stay, ICU mortality, and hospital mortality. The kinetics of different inflammatory (interleukin-1β, interleukin-6, interleukin-10, and C-reactive protein) and brain-related biomarkers (brain-derived neurotrophic factor and S-100B) were used as exploratory outcomes.

Results

A total of 160 patients were randomized, but one patients on the placebo group died before treatment, thus 159 patients were analyzed (minocycline, n=84; placebo, n=75). After the COVID-19 pandemic it was decided to early stop patient inclusion. There was a small but significant decrease in delirium incidence (17 (20%) patients in the minocycline arm compared to 26 (35%) patients in the placebo arm, P=0.043). No other delirium-related outcomes were modified by minocycline treatment. Unexpectedly, there was a significant decrease in hospital mortality (39% vs. 23%, P=0.029). Among all analyzed biomarkers, only plasma levels of C-reactive protein decreased significantly after minocycline treatment (F=0.75, P=0.78 within time; F=4.09, P=0.045 group⋅time).

Interpretation

Our findings in this rather small study signals a possible positive effect of minocycline on delirium incidence. Further studies are needed to confirm the benefits of this drug as a preventive measure in critically ill patients.

Clinical Trial Registration

NCT04219735

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预防性二甲胺四环素治疗危重患者谵妄:一项随机对照试验
背景:谵妄是一种潜在的严重急性脑病。米诺环素在神经系统疾病动物模型中具有神经保护作用;然而,来自人体研究的数据仍然很少。米诺环素的神经保护作用是否能预防危重病人谵妄的发生?研究设计和方法本研究是一项随机、安慰剂对照、双盲试验,在4个重症监护病房(icu)进行。年龄在18岁或以上的患者被随机接受米诺环素(100mg,每天两次)或安慰剂。主要观察指标为28天内或出院前谵妄发生率。次要结局包括ICU住院期间谵妄天数、无谵妄/昏迷天数、机械通气时间、ICU住院时间、ICU死亡率和住院死亡率。不同炎症(白细胞介素-1β、白细胞介素-6、白细胞介素-10和c反应蛋白)和脑相关生物标志物(脑源性神经营养因子和S-100B)的动力学被用作探索性结果。结果共纳入160例患者,安慰剂组1例患者在治疗前死亡,共分析159例患者(米诺环素,n=84;安慰剂,n = 75)。在2019冠状病毒病大流行之后,决定提前停止患者纳入。米诺环素组谵妄发生率虽小但显著降低(17例(20%),安慰剂组26例(35%),P=0.043)。米诺环素治疗未改变其他谵妄相关结果。出乎意料的是,住院死亡率显著下降(39%对23%,P=0.029)。在所有分析的生物标志物中,只有血浆c反应蛋白水平在米诺环素治疗后显著降低(F=0.75, P=0.78);F=4.09, P=0.045组⋅时间)。解释:我们在这项相当小的研究中的发现表明二甲胺四环素对谵妄发生率可能有积极作用。需要进一步的研究来证实这种药物作为危重患者预防措施的益处。临床试验注册号nct04219735
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来源期刊
Chest
Chest 医学-呼吸系统
CiteScore
13.70
自引率
3.10%
发文量
3369
审稿时长
15 days
期刊介绍: At CHEST, our mission is to revolutionize patient care through the collaboration of multidisciplinary clinicians in the fields of pulmonary, critical care, and sleep medicine. We achieve this by publishing cutting-edge clinical research that addresses current challenges and brings forth future advancements. To enhance understanding in a rapidly evolving field, CHEST also features review articles, commentaries, and facilitates discussions on emerging controversies. We place great emphasis on scientific rigor, employing a rigorous peer review process, and ensuring all accepted content is published online within two weeks.
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