Levosimendan Reduces Mortality and Postoperative Acute Kidney Injury in High-Risk Cardiac Surgery Patients: A Meta-analysis of 3,130 Patients

Objectives: The calcium sensitizer levosimendan increases cardiac contractility without increasing intracellular calcium or oxygen consumption and induces vasodilation. Levosimendan has already shown favorable hemodynamic effects in patients with acute heart failure. In this meta-analysis we aimed to determine the current evidence for administration of levosimendan in high-risk patients undergoing cardiac surgery.

Methods: We performed a meta-analysis of randomized controlled trials (RCT) and observational trials (OT) retrieved from a literature search in PubMed, EMBASE and Cochrane Library. Only the trials comparing the administration of levosimendan in cardiac surgery patients with a control group (treated with another inotrope, standard of care or an intra-aortic balloon pump (IABP)) were included. In addition at least one clinical outcome had to be mentioned: mortality, myocardial infarction, low cardiac output syndrome, stroke, acute kidney injury, dialysis, atrial fibrillation, prolonged inotropic support, length of ICU and hospital stay. The pooled treatment effects (odds ratio (OR), 95%-confidence intervals (95%-CI)) were assessed using a fixed or random effects model.

Results: The literature search retrieved a total of 35 trials (24 RCT, 10 OT, 1 pilot study) involving 3,130 cardiac surgery patients. Levosimendan was administered in 1574 patients (50.3%) and 1556 patients (49.7%) received the standard or control treatment. Patients treated with levosimendan showed a significantly reduced mortality (OR: 0.68; 95%-CI:0.50–0.92; p = 0.01). Furthermore levosimendan seems to restore adequate organ perfusion, as postoperative acute kidney injury was significantly decreased in the levosimendan group (18%) compared with control group (22%) (OR: 0.62; 95%-CI: 0.47–0.84; p = 0.002). However, with regard to subgroup analysis no statistical differences were found between the levosimendan group compared with IABP group due to small study sizes. Compared with standard therapy levosimendan seems to be beneficial in the following endpoints: mortality, low cardiac output syndrome, acute kidney injury, postoperative dialysis and prolonged inotropic support.

Conclusion: Current evidence from RCT and OT suggests beneficial effects for the perioperative administration of levosimendan in high-risk patients undergoing cardiac surgery.