Effects of levosimendan on mortality in patients with septic shock: systematic review with meta-analysis and trial sequential analysis

Object: Several studies have investigated a survival benefit for levosimendan treatment in patients with septic shock. However, data are conflicting. We conducted a meta-analysis to evaluate the effect of levosimendan treatment on mortality in patients with septic shock. Materials and Methods: We searched PubMed, EMBASE and Cochrane Library Databases up to March 27, 2017, without language restrictions. We searched for terms related to septic shock, levosimendan, randomized clinical trial. Randomized controlled trials reported the effect of levosimendan on mortality were included. Moreover, we constructed the trial sequential analysis (TSA) to determine the reliability of the outcomes. Furthermore, secondary outcomes were cardiac index(CI), mean arterial pressure (MAP), blood lactate, norepinephrine dose and length of ICU stay. Results: Ten studies with a total of 816 patients were included in this meta-analysis. There was no significant difference in the mortality between the levosimendan group and the standard inotropic therapy group [RR = 0.96, 95% CI (0.81-1.12), I-2 = 0]. However, methods adapted from formal interim monitoring boundaries applied to TSA indicated that the cumulative evidence was unreliable and inconclusive. Blood lactate was significantly reduced in the levosimendan group while there was no difference in MAP, CI, norepinephrine dose and length of ICU stay. Conclusions: Findings from this meta-analysis demonstrated that levosimendan treatment may not reduce mortality in patients with septic shock. The result remains inclusive and further randomized controlled trials were needed to confirm these conclusions.