DataSheet1_Efficacy and safety of levosimendan in patients with sepsis: a systematic review and network meta-analysis.docx

Objective: We conducted a systematic review to assess the advantages and disadvantages of levosimendan in patients with sepsis compared with placebo, milrinone, and dobutamine and to explore the clinical efficacy of different concentrations of levosimendan.
Methods: PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang data, VIP, and CBM databases were searched using such keywords as simendan, levosimendan, and sepsis. The search time was from the establishment of the database to July 2023. Two researchers were responsible for literature screening and data collection respectively. After the risk of bias in the included studies was evaluated, network meta-analysis was performed using R software gemtc and rjags package.
Results: Thirty-two randomized controlled trials (RCTs) were included in the network meta-analysis. Meta-analysis results showed that while levosimendan significantly improved CI levels at either 0.1 µg/kg/min (mean difference [MD] [95%CrI] = 0.41 [−0.43, 1.4]) or 0.2 µg/kg/min (MD [95%CrI] =0.54 [0.12, 0.99]). Levosimendan, at either 0.075 µg/kg/min (MD [95% CrI] =0.033 [−0.75, 0.82]) or 0.2 µg/kg/min (MD [95% CrI] = −0.014 [−0.26, 0.23]), had no significant advantage in improving Lac levels. Levosimendan, at either 0.1 µg/kg/min (RR [95% CrI] = 0.99 [0.73, 1.3]) or 0.2 µg/kg/min (RR [95% CrI] = 1.0 [0.88, 1.2]), did not have a significant advantage in reducing mortality.
Conclusion: The existing evidence suggests that levosimendan can significantly improve CI and lactate levels in patients with sepsis, and levosimendan at 0.1 µg/kg/min might be the optimal dose. Unfortunately, all interventions in this study failed to reduce the 28-day mortality.
Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441220.

研究目的：本研究开展系统综述，旨在评估左西孟旦（levosimendan）应用于脓毒症患者时，与安慰剂、米力农、多巴酚丁胺相比的优劣，并探讨不同给药浓度左西孟旦的临床疗效。
研究方法：检索PubMed、Web of Science、Cochrane图书馆、Embase、中国知网（CNKI）、万方数据、维普资讯（VIP）以及中国生物医学文献数据库（CBM），检索关键词包括simendan、左西孟旦（levosimendan）、脓毒症。检索时限为各数据库建库至2023年7月。由2名研究者分别负责文献筛选与数据采集。在对纳入研究的偏倚风险进行评估后，采用R软件的gemtc与rjags包开展网络Meta分析。
研究结果：本次网络Meta分析共纳入32项随机对照试验（randomized controlled trial, RCT）。Meta分析结果显示：当给药剂量为0.1 µg/kg/min时（均数差（Mean Difference, MD）[95%可信区间（Credible Interval, CrI）] = 0.41 [-0.43, 1.4]）或0.2 µg/kg/min时（均数差（MD）[95%CrI] = 0.54 [0.12, 0.99]），左西孟旦均可显著改善心脏指数（Cardiac Index, CI）水平；当给药剂量为0.075 µg/kg/min时（均数差（MD）[95%CrI] = 0.033 [-0.75, 0.82]）或0.2 µg/kg/min时（均数差（MD）[95%CrI] = -0.014 [-0.26, 0.23]），左西孟旦在改善乳酸（Lactate, Lac）水平方面未展现出显著优势。当给药剂量为0.1 µg/kg/min时（相对风险（Relative Risk, RR）[95%CrI] = 0.99 [0.73, 1.3]）或0.2 µg/kg/min时（相对风险（RR）[95%CrI] = 1.0 [0.88, 1.2]），左西孟旦在降低死亡率方面未展现出显著优势。
研究结论：现有证据表明，左西孟旦可显著改善脓毒症患者的心脏指数与乳酸水平，其中0.1 µg/kg/min剂量的左西孟旦或许为最优给药剂量。遗憾的是，本研究纳入的所有干预措施均未能降低28天死亡率。
系统综述注册信息：https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441220