Table_1_Clinical Multi-Omics Study on the Gut Microbiota in Critically Ill Patients After Cardiovascular Surgery Combined With Cardiopulmonary Bypass With or Without Sepsis (MUL-GM-CSCPB Study): A Prospective Study Protocol.pdf

Introduction: Fever of unknown origin (FUO) and hemodynamic instability are complications that develop after cardiac surgery combined with cardiopulmonary bypass (CPB) for heart disease. Patients who develop fever with hemodynamic instability after cardiac surgery may have systemic inflammatory response syndrome or sepsis. Cardiopulmonary bypass (CPB) is a technique that temporarily takes over the function of the heart and lungs during cardiac surgery. Recent reports suggest that early bloodstream infections of patients undergoing CPB are due to gram-negative bacteria that are present in the intestinal flora. The theory of intestinal flora translocation has growing evidence. Intestinal ischemia-reperfusion that occurs during cardiac surgery with CPB will induce a systemic inflammatory reaction and may cause intestinal flora translocation. Does this systemic reaction cause sepsis? We therefore propose this protocol to determine whether the changes in the intestinal flora in patients after cardiac surgery with CPB are related to sepsis.Methods and Analysis: This study is a prospective observational case–control study to analyze the variation in the intestinal microflora and metabolites in patients undergoing cardiac surgery with CPB and to observe the outcomes of patients with routine clinical interventions. The control group will include healthy people without intestinal illness. Feces and blood samples will be acquired 1 day before cardiac surgery and within 24–72 h after cardiac surgery, and will be used for genomics and metabolomics analyses. Demographic data describing age, sex, main diagnosis, and past medical history and data related to the CPB time and application of antibiotics are available. Sequential (sepsis-related) organ failure assessment, infection-related laboratory items, infection site, and pathogenic microorganisms, and nutrition, and gastrointestinal function assessment are additionally recorded. Group analysis of data will be conducted according to the outcomes (sepsis vs. non-sepsis and survivors vs. non-survivors).Ethics and Dissemination: This protocol has been ethically approved by the Ethics Committee of Peking Union Medical College (ID: ZS-1612). Informed consent will be obtained before subject enrolment, and data will be stored in a secured database. The results will be submitted to international peer-reviewed journals and presented at international conferences.Trial Registration Number: NCT04032938.

引言：在心脏疾病手术中，联合使用心肺旁路术（CPB）后，不明原因发热（FUO）及血流动力学不稳定是可能出现的并发症。心脏手术后出现发热伴随血流动力学不稳定症状的患者，可能患有全身性炎症反应综合征或败血症。心肺旁路术（CPB）是一种在心脏手术期间暂时接管心脏和肺功能的技术。近期研究指出，接受CPB手术的患者早期血液感染是由存在于肠道菌群中的革兰氏阴性菌引起的。肠道菌群易位理论逐渐获得支持证据。在心肺旁路术（CPB）下进行心脏手术时发生的肠道缺血再灌注，将引发全身性炎症反应，并可能导致肠道菌群易位。这种全身性反应是否会引发败血症？鉴于此，本研究协议旨在确定心脏手术后接受CPB治疗的患者肠道菌群的变化是否与败血症相关。方法与分析：本研究是一项前瞻性观察性病例对照研究，旨在分析接受CPB心脏手术患者肠道微生物群和代谢物的变化，并观察常规临床干预措施对患者的结局影响。对照组将包括无肠道疾病的健康个体。将在心脏手术前1天和手术后24至72小时内采集粪便和血液样本，用于基因组学和代谢组学分析。可获取描述年龄、性别、主要诊断以及既往病史的人口统计学数据，以及与CPB时间和抗生素应用相关的数据。此外，还将记录序贯（败血症相关）器官功能衰竭评估、感染相关实验室指标、感染部位、致病微生物、营养状况及胃肠道功能评估。根据结局（败血症与非败血症以及存活者与非存活者）进行分组数据分析。伦理与传播：本协议已获得北京大学医学部伦理委员会的伦理批准（ID：ZS-1612）。在主体招募前将获得知情同意，数据将存储在安全数据库中。结果将提交至国际同行评审期刊，并在国际会议上展示。临床试验注册号：NCT04032938。