Levosimendan to Facilitate Weaning From ECMO in Patients With Severe Cardiogenic Shock: The LEVOECMO Randomized Clinical Trial.

Background

To assess whether early administration of levosimendan reduces the time to successful VA-ECMO weaning in patients with severe but potentially reversible cardiogenic shock.

评估早期使用左西孟旦是否能减少严重但潜在可逆性心源性休克患者成功脱机 VA-ECMO 的时间。

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlledtrial conducted across 11 intensive care units (ICUs) in France.

设计、环境和参与者：在法国11个重症监护病房（ICU）进行的随机、双盲、安慰剂对照试验。

Between August 27, 2021, and September 10, 2024, 205 adult patients with acute cardiogenic shock who had started VA-ECMO in the preceding 48 hours were enrolled.

在2021年8月27日至2024年9月10日期间，共有205名在过去48小时内开始使用VA-ECMO的急性心源性休克成年患者被纳入研究。

Final follow-up was completed on November 10, 2024.

最终随访完成于2024年11月10日。

Methods

Patients were randomized in a 1:1 ratio to receive levosimendan, 0.15 μg/kg per minute, to be increased to 0.20 μg/kg per minute after 2 hours (n = 101), or placebo (n = 104).

患者按1:1的比例随机分配接受左西孟旦，起始剂量为每分钟0.15微克/千克，2小时后增加至每分钟0.20微克/千克（n = 101），或安慰剂（n = 104）。

main_outcomes_and_measures

The primary outcome was time to successful ECMO weaning within 30 days following randomization.

主要结果是在随机化后30天内成功脱离ECMO的时间。

Secondary outcomes included ECMO-, mechanical ventilation-, and organ failure-free days, ICU and hospital lengths of stay, serious adverse events, and all-cause 30- and 60-day mortality.

次要结果包括ECMO、机械通气和器官衰竭的无天数，ICU和医院的住院时间，严重不良事件以及30天和60天的全因死亡率。

Results

Among the 205 randomized patients (median age, 58 [IQR, 50-67] years; 149 [72.7%] male), main cardiogenic shock etiologies were postcardiotomy (79 [38.5%]), acute myocardial infarction (56 [27.3%]), and myocarditis (28 [13.7%]).

在205名随机患者中（中位年龄58岁，四分位数间距[50-67]岁；149名[72.7%]为男性），主要的心源性休克病因包括术后（79名[38.5%]）、急性心肌梗死（56名[27.3%]）和心肌炎（28名[13.7%]）。

Treatment dose was increased to 0.20 ± 0.01 μg/kg per minute in 93% of patients receiving levosimendan and in 96% of those receiving placebo.

在接受左西孟旦治疗的患者中，93%的剂量增加到每分钟0.20 ± 0.01微克/公斤，在接受安慰剂治疗的患者中，96%的剂量增加到相同水平。

Within 30 days, 69 of 101 patients (68.3%) had a successful ECMO weaning in the levosimendan group compared with 71 of 104 (68.3%) in the placebo group (risk difference, 0.0% [95% CI, -12.8% to 12.7%]; subdistribution hazard ratio, 1.02 [95% CI, 0.74-1.39]; P = .92).

在30天内，101名患者中有69名（68.3%）在左西孟旦组成功脱离ECMO，而在安慰剂组的104名患者中有71名（68.3%）成功脱离ECMO（风险差异，0.0% [95% 置信区间，-12.8% 至 12.7%]；亚分布风险比，1.02 [95% 置信区间，0.74-1.39]；P = .92）。

In the levosimendan and placebo groups, respectively, median ECMO duration (5 [IQR, 4-7] days vs 6 [IQR, 4-11] days; P = .53), mean ICU length of stay (18 [SD, 15] days vs 19 [SD, 15] days; P = .42), and 60-day mortality (27.7% vs 25.0%; risk difference, 2.7% [95% CI, -9.0% to 15.3%]; P = .78) did not differ significantly.

在左西孟旦组和安慰剂组中，ECMO的中位持续时间（5 [四分位数间距，4-7] 天 vs 6 [四分位数间距，4-11] 天；P = .53）、平均ICU住院时间（18 [标准差，15] 天 vs 19 [标准差，15] 天；P = .42）以及60天的死亡率（27.7% vs 25.0%；风险差异，2.7% [95% 置信区间，-9.0% 至 15.3%]；P = .78）没有显著差异。

Ventricular arrhythmias occurred more frequently with levosimendan (18 [17.8%] vs 9 [8.7%]; absolute risk difference, 9.2% [95% CI, 0.4%-18.1%]).

左西孟旦治疗组的室性心律失常发生率更高（18 [17.8%] vs 9 [8.7%]；绝对风险差异，9.2% [95% 置信区间，0.4%-18.1%]）。

conclusions_and_relevance

Among patients with severe but potentially reversible cardiogenic shock supported by VA-ECMO, early levosimendan administration did not significantly reduce the time to successful weaning of ECMO compared with placebo.

在使用VA-ECMO支持的严重但潜在可逆的心源性休克患者中，早期使用左西孟旦与安慰剂相比，并没有显著缩短成功撤除ECMO的时间。

trial_registration

ClinicalTrials.gov Identifier: NCT04728932.

临床试验注册号：NCT04728932。