Key result
Levosimendan at 0.2 µg/kg/min significantly improved cardiac index compared to placebo (MD 0.54) in patients with sepsis, though no dose reduced 28-day mortality.
Why the study?
The comparative advantages, disadvantages, and dose-dependent clinical efficacy of levosimendan versus placebo, milrinone, and dobutamine in sepsis were unclear.
Does levosimendan improve cardiac index and reduce mortality in adult patients with sepsis compared to placebo, milrinone, or dobutamine?
Systematic Review (n=2,813)
Does levosimendan improve cardiac index and reduce mortality in adult patients with sepsis compared to placebo, milrinone, or dobutamine?
Mean Difference: 0.54 (95% CI 0.12–0.99)
In patients with sepsis, levosimendan improves cardiac index and lactate levels, with 0.1 µg/kg/min appearing to be the optimal dose, but it does not reduce 28-day mortality.
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 .
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Tan et al. (2024) conducted a systematic review in Sepsis or septic shock (n=2,813). Levosimendan vs. Placebo, dobutamine, or milrinone was evaluated on Cardiac index (CI) (MD 0.54, 95% CI 0.12-0.99). Levosimendan at 0.2 µg/kg/min significantly improved cardiac index compared to placebo (MD 0.54) in patients with sepsis, though no dose reduced 28-day mortality.
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