Felipe Dal-Pizzol, André Coelho, Carla S. Simon, Monique Michels, Emily Corneo, Aline Jeremias, Danusa Damásio, Cristiane Ritter
{"title":"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","authors":"Felipe Dal-Pizzol, André Coelho, Carla S. Simon, Monique Michels, Emily Corneo, Aline Jeremias, Danusa Damásio, Cristiane Ritter","doi":"10.1016/j.chest.2023.11.041","DOIUrl":null,"url":null,"abstract":"<h3>Background</h3><p>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.</p><h3>Research Question</h3><p>Does the neuroprotective effect of minocycline prevent delirium occurrence in critical ill patients?</p><h3>Study design and Methods</h3><p>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.</p><h3>Results</h3><p>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, <em>P</em>=0.043). No other delirium-related outcomes were modified by minocycline treatment. Unexpectedly, there was a significant decrease in hospital mortality (39% vs. 23%, <em>P</em>=0.029). Among all analyzed biomarkers, only plasma levels of C-reactive protein decreased significantly after minocycline treatment (F=0.75, <em>P</em>=0.78 within time; F=4.09, <em>P</em>=0.045 group⋅time).</p><h3>Interpretation</h3><p>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.</p><h3>Clinical Trial Registration</h3><p>NCT04219735</p>","PeriodicalId":9782,"journal":{"name":"Chest","volume":"122 18","pages":""},"PeriodicalIF":9.5000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prophylactic minocycline for delirium in critically ill patients: a randomized controlled trial\",\"authors\":\"Felipe Dal-Pizzol, André Coelho, Carla S. Simon, Monique Michels, Emily Corneo, Aline Jeremias, Danusa Damásio, Cristiane Ritter\",\"doi\":\"10.1016/j.chest.2023.11.041\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3>Background</h3><p>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.</p><h3>Research Question</h3><p>Does the neuroprotective effect of minocycline prevent delirium occurrence in critical ill patients?</p><h3>Study design and Methods</h3><p>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.</p><h3>Results</h3><p>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, <em>P</em>=0.043). No other delirium-related outcomes were modified by minocycline treatment. Unexpectedly, there was a significant decrease in hospital mortality (39% vs. 23%, <em>P</em>=0.029). Among all analyzed biomarkers, only plasma levels of C-reactive protein decreased significantly after minocycline treatment (F=0.75, <em>P</em>=0.78 within time; F=4.09, <em>P</em>=0.045 group⋅time).</p><h3>Interpretation</h3><p>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.</p><h3>Clinical Trial Registration</h3><p>NCT04219735</p>\",\"PeriodicalId\":9782,\"journal\":{\"name\":\"Chest\",\"volume\":\"122 18\",\"pages\":\"\"},\"PeriodicalIF\":9.5000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chest\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.chest.2023.11.041\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CRITICAL CARE MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chest","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.chest.2023.11.041","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CRITICAL CARE MEDICINE","Score":null,"Total":0}
Prophylactic minocycline for delirium in critically ill patients: a randomized controlled trial
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
