Levosimendan for Prevention of Acute Kidney Injury After Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials

Background: Levosimendan has been shown to confer direct renoprotection in renal endotoxemic and ischemia-reperfusion injury and could increase renal blood flow in patients with low-cardiac-output heart failure. Results from clinical trials of levosimendan on acute kidney injury (AKI) following cardiac surgery are controversial.

Study design: A random-effect meta-analysis was conducted based on evidence from PubMed, EMBASE, and Cochrane Library.

Settings & population: Adult patients undergoing cardiac surgery.

Selection criteria for studies: Randomized controlled trials comparing the renal effect of levosimendan versus placebo or other inotropic drugs during cardiac surgery.

Intervention: Perioperative levosimendan continuous infusion at a rate of 0.1 to 0.2μg/kg/min following a loading dose (6-24μg/kg) for 24 hours or only 1 loading dose (24μg/kg) within 1 hour.

Outcomes: AKI, need for renal replacement therapy, mechanical ventilation duration, intensive care unit stay during hospitalization, and postoperative mortality (in-hospital or within 30 days).

Results: 13 trials with a total of 1,345 study patients were selected. Compared with controls, levosimendan reduced the incidence of postoperative AKI (40/460 vs 78/499; OR, 0.51; 95% CI, 0.34-0.76; P=0.001; I(2)=0.0%), renal replacement therapy (22/492 vs 49/491; OR, 0.43; 95% CI, 0.25-0.76; P=0.002; I(2)=0.0%), postoperative mortality (35/658 vs 94/657; OR, 0.41; 95% CI, 0.27-0.62; P<0.001; I(2)=0.0%), mechanical ventilation duration (in days; n=235; weighted mean difference, -0.34; 95% CI, -0.58 to -0.09; P=0.007], and intensive care unit stay (in days; n=500; weighted mean difference, -2.2; 95% CI, -4.21 to -0.13; P=0.04).

Limitations: Different definitions for AKI among studies. Small sample size for some trials.

Conclusions: Perioperative administration of levosimendan in patients undergoing cardiac surgery may reduce complications. Future trials are needed to determine the dose effect of levosimendan in improving outcomes, especially in patients with decreased baseline kidney function.