Effects of levosimendan on weaning and survival in adult cardiogenic shock patients with veno-arterial extracorporeal membrane oxygenation: systematic review and meta-analysis

Introduction: Veno-arterial extracorporeal membrane oxygenation may be used to support patients with refractory cardiogenic shock. Many patients can be successfully weaned, the ability of some medications to facilitate weaning from veno-arterial extracorporeal membrane oxygenation were reported. To date, there are limited studies investigating the impact of levosimendan on veno-arterial extracorporeal membrane oxygenation weaning. The objective of this systematic review and meta-analysis was to assess the effects of levosimendan on successful weaning from veno-arterial extracorporeal membrane oxygenation and survival in adult patients with cardiogenic shock. Methods: We performed a systematic review and meta-analysis (PubMed, the Cochrane Library, and the International Clinical Trials Registry Platform published from the year 2000 onwards) investigating whether levosimendan offers advantages compared to standard therapy or placebo, in cardiogenic shock adult patients treated with veno-arterial extracorporeal membrane oxygenation. The primary outcome was veno-arterial extracorporeal membrane oxygenation successful weaning, whereas secondary outcome was all-cause mortality at the longest follow-up available. We pooled risk ratio and 95% confidence interval using fixed and random effects models according to the heterogeneity. Results: A total of five non-randomized clinical trials comprising 557 patients were included, 299 patients for levosimendan and 258 patients for control groups. The pooled prevalence of veno-arterial extracorporeal membrane oxygenation successful weaning was 61.4% (95% confidence interval 39.8-82.9%), and all-cause mortality was 36% (95% confidence interval 29.6-48.8%). There was a significant increase in veno-arterial extracorporeal membrane oxygenation successful weaning with levosimendan compared to the controls (risk ratio = 1.42 (95% confidence interval 1.12-1.8), p for effect = 0.004, I² = 71%). A decrease risk of all-cause mortality in the levosimendan group was also observed, risk ratio = 0.62 (95% confidence interval 0.44-0.88), p for effect = 0.007, I² = 36%. Conclusion: The use of levosimendan on adult patients with cardiogenic shock may facilitate the veno-arterial extracorporeal membrane oxygenation weaning and reduce all-cause mortality. Few articles of this topic are available, and prospective, randomized multi-center trials are warranted to conclude decisively on the benefits of levosimendan in this setting.