ICM:兰地洛尔用于脓毒症休克持续性心动过速患者的心率控制:一项多中心随机临床试验

Abstract

Purpose: 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.

目的：复苏后的脓毒性休克患者如果心动过速过度，可能会损害血流动力学并恶化患者的预后。我们研究了是否能够在不增加血管活性药物需求的情况下，通过使用可滴定的高选择性、超短效β1阻滞剂兰地洛尔来控制心率（HR）。

Methods: 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.

方法：这项随机、开放标签、对照试验在2018年至2022年在7个欧洲国家的20个地点进行，研究了兰地洛尔在成年脓毒性休克和持续性心动过速患者中的疗效和安全性。患者被随机分配接受兰地洛尔加上标准治疗（n = 99）或单独标准治疗（n = 101）。联合主要终点是心率反应（即心率在每分钟80-94次的范围内）及其在治疗开始后前24小时内无需增加血管活性药物需求的维持。关键次要终点是28天死亡率和不良事件。

Results: 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.

结果：在196名纳入的脓毒性休克患者中，98名接受了兰地洛尔加标准治疗，98名接受了单独的标准治疗。兰地洛尔组中达到联合主要终点的患者比例显著高于对照组（39.8% [39/98] 对比 23.5% [23/98]），两组之间的差异为16.5%（95%置信区间[CI]：3.4-28.8%；p = 0.013）。在测试的次要结果和不良事件方面，研究组之间没有统计学上的显著差异。

Conclusion: 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. 

结论：超短效β阻滞剂兰地洛尔在不增加血管活性药物需求的情况下，有效降低并维持脓毒性休克和持续性心动过速患者的心率。与标准治疗相比，不良事件和临床结果（如28天死亡率）没有差异。在先前试验的背景下，这项研究的结果不支持在未经选择的持续性心动过速的脓毒性休克患者群体中采用严格的心率降低（<95次/分钟）的治疗策略。需要进一步的研究来识别从心率控制中获得临床益处的脓毒性休克患者表型。