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 ChinaThese authors contributed equally to this workCorrespondence: 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.comPurpose: One-hour sepsis bundle was developed in 2018. However, the optimal timing for antibiotic, fluid resuscitation, and vasopressor initiation in intensive care units (ICUs) remains debated. High-quality randomized evidence is limited, particularly for ICU patients. Therefore, we emulated three target trials using observational data.Patients and Methods: We conducted a retrospective, multicenter cohort study using data from the Medical Information Mart for Intensive Care-IV database (primary dataset), and two ICU cohorts from China (Zhujiang and Xiangya hospitals). Within a target trial emulation framework with inverse probability of treatment weighting, we constructed three two-arm trials comparing initiation of (1) antibiotics, (2) fluid resuscitation, and (3) vasopressors within 0– 1 hour versus 1– 3 hours after a prespecified time zero.Results: In the target trial emulations, antibiotic initiation within 1 hour was associated with lower 28-day mortality (HR 0.65; 95% CI 0.54– 0.79) and earlier ICU discharge (competing-risk analysis; SHR 1.20; 95% CI 1.12– 1.27) compared with initiation at 1– 3 hours. For fluid resuscitation, initiating within 1 hour and delivering ≥ 30 mL/kg crystalloid within 3 hours resulted in lower mortality (HR 0.72; 95% CI 0.53– 0.97) and earlier discharge (SHR 1.17; 95% CI 1.02– 1.33). However, vasopressor initiation within 1 hour showed no survival benefit (HR 1.07; 95% CI 0.89– 1.29) or reduction in time to ICU discharge (SHR 1.02; 95% CI 0.95– 1.08). These findings remained consistent across sensitivity and subgroup analyses, including comparisons using a 1– 6 hour window.Conclusion: In ICUs, early administration of antibiotics and initiation of fluid resuscitation within 1 hour were associated with improved survival and earlier ICU discharge, whereas early vasopressor use was not. These findings might support a bedside emphasis on timely antibiotics and fluids during early resuscitation and provide evidence for refining time targets in future sepsis guidelines.Keywords: sepsis, septic shock, antibiotic, fluid resuscitation, vasopressor
M et al. (Thu,) studied this question.