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已发表论文
危重症患者中脓毒症集束化治疗核心要素的启动时机：一项多中心目标模拟试验研究
Authors Li M , Zhang J, Huang H , Li J , Zhang B, Zhao S, Peng Z, Han S, Guan J, Yang J, Wang G, Chang Y, Chang P, Yu Z, Zhong T, Liu Z
Received 12 December 2025
Accepted for publication 15 January 2026
Published 23 January 2026 Volume 2026:18 588212
DOI https://doi.org/10.2147/CLEP.S588212
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Thomas Ahern
Mingxia Li,1,* Jiaqi Zhang,2,* Haozhao Huang,1,* Jiamin Li,1,* Buyao Zhang,3 Shuangping Zhao,3 Zishan Peng,1 Shuzhe Han,4 Jianbin Guan,1 Jingjing Yang,1 Guizhong Wang,1 Yuan Chang,5 Ping Chang,1 Zhaoxian Yu,6 Tao Zhong,1 Zhanguo Liu1
1Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Nutrition and Obstetrics and Gynecology, 967th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Dalian, Liaoning, People’s Republic of China; 5Department of Gastrointestinal Electrophysiology, College of Medicine, Chosun University, Gwangju, Republic of Korea; 6State Key Laboratory of Respiratory Disease, Institute of Tuberculosis, Guangzhou Medical University and Guangzhou Chest Hospital Affiliated to Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zhanguo Liu, Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China, Email zhguoliu@163.com Ping Chang, Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China, Email changp963@163.com
摘要
目的： 2018年，拯救脓毒症运动提出脓毒症1小时集束化治疗。然而，抗生素、液体复苏及血管升压药在重症监护病房的最佳启动时机仍存争议。特别是针对危重症患者的高质量随机对照试验较少。因此，我们利用观察性数据模拟了三项目标试验进行探索。
患者与方法： 我们采用了回顾性、多中心队列研究设计，数据来源于美国重症监护医学信息集市IV数据库（主要数据集）及中国两家医院（珠江医院与湘雅医院）的ICU队列。在应用治疗逆概率加权的目标模拟试验框架下，我们构建了三组双臂试验，分别比较在预设零时点后（1）抗生素、（2）液体复苏、（3）血管升压药在0-1小时内启动与 1-3小时内启动的差异。
结果： 在目标模拟试验中，与1-3小时内启动相比，1小时内启动抗生素与较低的28天死亡率（HR 0.65；95% CI 0.54–0.79）和更早的ICU转出（竞争风险分析；SHR 1.20；95% CI 1.12–1.27）相关。对于液体复苏，1小时内启动并在3小时内给予≥30 mL/kg晶体液，可降低死亡率（HR 0.72；95% CI 0.53–0.97）并促进更早转出（SHR 1.17；95% CI 1.02–1.33）。然而，1小时内启动血管升压药未显示生存获益（HR 1.07；95% CI 0.89–1.29），也未缩短ICU住院时间（SHR 1.02；95% CI 0.95–1.08）。上述发现与敏感性分析及亚组分析结果一致，包括采用 1–6 小时扩展窗口的敏感性分析。
结论： 在ICU中，1小时内给予抗感染药物和启动液体复苏与改善生存及更早ICU转出相关，而早期启动血管升压药未显示获益。本研究结果提示，早期复苏的床旁管理应重点强调及时抗生素与液体治疗，并为未来脓毒症指南中时间目标的优化提供证据。
关键词： 脓毒症；脓毒性休克；抗生素；液体复苏；血管升压药
1Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Internal Emergency Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Nutrition and Obstetrics and Gynecology, 967th Hospital of the Joint Logistics Support Force of the Chinese People’s Liberation Army, Dalian, Liaoning, People’s Republic of China; 5Department of Gastrointestinal Electrophysiology, College of Medicine, Chosun University, Gwangju, Republic of Korea; 6State Key Laboratory of Respiratory Disease, Institute of Tuberculosis, Guangzhou Medical University and Guangzhou Chest Hospital Affiliated to Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Zhanguo Liu, Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China, Email zhguoliu@163.com Ping Chang, Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China, Email changp963@163.com
摘要
目的： 2018年，拯救脓毒症运动提出脓毒症1小时集束化治疗。然而，抗生素、液体复苏及血管升压药在重症监护病房的最佳启动时机仍存争议。特别是针对危重症患者的高质量随机对照试验较少。因此，我们利用观察性数据模拟了三项目标试验进行探索。
患者与方法： 我们采用了回顾性、多中心队列研究设计，数据来源于美国重症监护医学信息集市IV数据库（主要数据集）及中国两家医院（珠江医院与湘雅医院）的ICU队列。在应用治疗逆概率加权的目标模拟试验框架下，我们构建了三组双臂试验，分别比较在预设零时点后（1）抗生素、（2）液体复苏、（3）血管升压药在0-1小时内启动与 1-3小时内启动的差异。
结果： 在目标模拟试验中，与1-3小时内启动相比，1小时内启动抗生素与较低的28天死亡率（HR 0.65；95% CI 0.54–0.79）和更早的ICU转出（竞争风险分析；SHR 1.20；95% CI 1.12–1.27）相关。对于液体复苏，1小时内启动并在3小时内给予≥30 mL/kg晶体液，可降低死亡率（HR 0.72；95% CI 0.53–0.97）并促进更早转出（SHR 1.17；95% CI 1.02–1.33）。然而，1小时内启动血管升压药未显示生存获益（HR 1.07；95% CI 0.89–1.29），也未缩短ICU住院时间（SHR 1.02；95% CI 0.95–1.08）。上述发现与敏感性分析及亚组分析结果一致，包括采用 1–6 小时扩展窗口的敏感性分析。
结论： 在ICU中，1小时内给予抗感染药物和启动液体复苏与改善生存及更早ICU转出相关，而早期启动血管升压药未显示获益。本研究结果提示，早期复苏的床旁管理应重点强调及时抗生素与液体治疗，并为未来脓毒症指南中时间目标的优化提供证据。
关键词： 脓毒症；脓毒性休克；抗生素；液体复苏；血管升压药