Rehberg Sebastian, Frank Sandra, Černý Vladimír, Cihlář Radek, Borgstedt Rainer, Biancofiore Gianni, Guarracino Fabio, Schober Andreas, Trimmel Helmut, Pernerstorfer Thomas, Siebers Christian, Dostál Pavel, Morelli Andrea, Joannidis Michael, Pretsch Ingrid, Fuchs Christian, Rahmel Tim, Podbregar Matej, Duliczki Éva, Tamme Kadri, Unger Martin, Sus Jan, Klade Christoph, Krejcy Kurt, Kirchbaumer-Baroian Nairi, Krumpl Günther, Duška František
Department of Anaesthesiology, Intensive Care, Emergency Medicine, Transfusion Medicine and Pain Therapy, University Hospital of Bielefeld, Bielefeld, Germany.
Department of Anaesthesiology, LMU University Hospital, LMU Munich, Munich, Germany.
Intensive Care Med. 2024 Oct;50(10):1622-1634. doi: 10.1007/s00134-024-07587-1. Epub 2024 Sep 19.
Excessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting β1-blocker landiolol.
This randomized, open-label, controlled trial was conducted at 20 sites in 7 European countries from 2018 to 2022 and investigated the efficacy and safety of landiolol in adult patients with septic shock and persistent tachycardia. Patients were randomly assigned to receive either landiolol along with standard treatment (n = 99) or standard treatment alone (n = 101). The combined primary endpoint was HR response (i.e., HR within the range of 80-94 beats per minute) and its maintenance without increasing vasopressor requirements during the first 24 h after treatment start. Key secondary endpoints were 28-day mortality and adverse events.
Out of 196 included septic shock patients, 98 received standard treatment combined with landiolol and 98 standard treatment alone. A significantly larger proportion of patients met the combined primary endpoint in the landiolol group than in the control group (39.8% [39/98] vs. 23.5% [23/98]), with a between-group difference of 16.5% (95% confidence interval [CI]: 3.4-28.8%; p = 0.013). There were no statistically significant differences between study groups in tested secondary outcomes and adverse events.
The ultra-short-acting beta-blocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. There were no differences in adverse events and clinical outcomes such as 28-day mortality vs. standard of care. The results of this study, in the context of previous trials, do not support a treatment strategy of stringent HR reduction (< 95 bpm) in an unselected septic shock population with persistent tachycardia. Further investigations are needed to identify septic shock patient phenotypes that benefit clinically from HR control.
复苏后的感染性休克患者出现过度心动过速会损害血流动力学并使患者预后恶化。我们研究了使用可滴定的高选择性、超短效β1受体阻滞剂兰地洛尔在不增加血管升压药用量的情况下是否能够实现心率（HR）控制。
这项随机、开放标签、对照试验于2018年至2022年在7个欧洲国家的20个地点进行，研究了兰地洛尔在患有感染性休克和持续性心动过速的成年患者中的疗效和安全性。患者被随机分配接受兰地洛尔联合标准治疗（n = 99）或仅接受标准治疗（n = 101）。联合主要终点是心率反应（即心率在每分钟80 - 94次范围内）及其在治疗开始后的前24小时内不增加血管升压药用量的维持情况。关键次要终点是28天死亡率和不良事件。
在196例纳入的感染性休克患者中，98例接受了标准治疗联合兰地洛尔，98例仅接受标准治疗。兰地洛尔组达到联合主要终点的患者比例显著高于对照组（39.8% [39/98] 对 23.5% [23/98]），组间差异为16.5%（95%置信区间[CI]：3.4 - 28.8%；p = 0.013）。在测试的次要结局和不良事件方面，研究组之间没有统计学上的显著差异。
超短效β受体阻滞剂兰地洛尔在感染性休克和持续性心动过速患者中，在24小时后可有效降低并维持心率，且不增加血管升压药用量。在不良事件和临床结局如28天死亡率与标准治疗方面没有差异。在之前试验的背景下，本研究结果不支持在未选择的持续性心动过速感染性休克人群中采取严格降低心率（< 95次/分钟）的治疗策略。需要进一步研究以确定从心率控制中临床获益的感染性休克患者表型。
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