Endo Akira, Yamakawa Kazuma, Tagami Takashi, Umemura Yutaka, Wada Takeshi, Yamamoto Ryo, Nagasawa Hiroki, Takayama Wataru, Yagi Masayuki, Takahashi Kyosuke, Kojima Mitsuaki, Narita Chihiro, Kazuma Satoshi, Takahashi Jiro, Shiraishi Atsushi, Todani Masaki, Nakane Masaki, Nagata Toshihiko, Tanaka Shohei, Yokokawa Yuta, Takahashi Kunihiko, Ishikita Haruka, Hisamune Ryo, Sasaki Junichi, Muramatsu Ken-Ichi, Sonobe Hiroyuki, Minami Kazunobu, Hoshi Hiromasa, Otomo Yasuhiro
Department of Acute Critical Care Medicine, Tsuchiura Kyodo General Hospital, Tsuchiura, Ibaraki, Japan.
Trauma and Acute Critical Care Center, Tokyo Medical and Dental University Hospital, 1-5-45 Yushima, Bunkyo, Tokyo, Japan.
Intensive Care Med. 2025 May 13. doi: 10.1007/s00134-025-07910-4.
We examined the effect of a high-target mean arterial pressure (MAP) on septic shock in a previously underrepresented region.
A multicentre, pragmatic, open-label, randomised controlled trial was conducted in 29 hospitals in Japan, where the prevalence of chronic hypertension among older individuals is 66.9%. Patients who were diagnosed with septic shock, aged ≥ 65 years, and admitted to an intensive care unit were randomised 1:1 to the high (target MAP = 80-85 mmHg) or control (target MAP = 65-70 mmHg) groups from 1 July 2021 to 12 December 2023. The target MAP was maintained for 72 h or until vasopressors were no longer required. The primary outcome was the 90-day all-cause mortality. Secondary outcomes included organ support-free days and adverse events.
The trial was terminated early on the basis of the interim analysis results, suggesting the harm of the high-target strategy. Of the 518 patients, 258 were in the high-target group, and 260 were in the control group. By 90 days after randomisation, 101 patients (39.3%) in the high-target group and 74 (28.6%) in the control group had died from any cause (risk difference = 10.7; 95% confidence interval, 2.6-18.9). Renal replacement therapy-free days at 28 days were shorter in the high-target group. No clinical benefits for any outcome were observed in any subpopulation, including those with known chronic hypertension.
Among older patients with septic shock, high-target MAP significantly increased mortality compared with standard care.
UMIN Clinical Trials Registry; UMIN000041775; 13 September 2020.
我们在一个先前研究较少的地区，研究了高目标平均动脉压（MAP）对感染性休克的影响。
在日本的29家医院进行了一项多中心、务实、开放标签、随机对照试验，该国老年人群中慢性高血压的患病率为66.9%。2021年7月1日至2023年12月12日期间，年龄≥65岁、被诊断为感染性休克并入住重症监护病房的患者被1:1随机分配至高目标组（目标MAP = 80 - 85 mmHg）或对照组（目标MAP = 65 - 70 mmHg）。目标MAP维持72小时或直至不再需要血管升压药。主要结局是90天全因死亡率。次要结局包括无器官支持天数和不良事件。
根据中期分析结果，试验提前终止，提示高目标策略有害。518例患者中，258例在高目标组，260例在对照组。随机分组后90天时，高目标组有101例患者（39.3%）因任何原因死亡，对照组有74例（28.6%）（风险差异 = 10.7；95%置信区间，2.6 - 18.9）。高目标组28天时无肾脏替代治疗天数较短。在任何亚组中，包括已知患有慢性高血压的亚组，均未观察到任何结局的临床益处。
在老年感染性休克患者中，与标准治疗相比，高目标MAP显著增加死亡率。
UMIN临床试验注册中心；UMIN000041775；2020年9月13日。
