Levosimendan for patients with severely reduced left ventricular systolic function and/or low cardiac output syndrome undergoing cardiac surgery: a systematic review and meta-analysis

Filippo Sanfilippo, Joshua B Knight, Sabino Scolletta, Cristina Santonocito, Federico Pastore, Ferdinando L Lorini, Luigi Tritapepe, Andrea Morelli, Antonio Arcadipane, Filippo Sanfilippo, Joshua B Knight, Sabino Scolletta, Cristina Santonocito, Federico Pastore, Ferdinando L Lorini, Luigi Tritapepe, Andrea Morelli, Antonio Arcadipane

Abstract

Background: Previous studies have shown beneficial effects of levosimendan in high-risk patients undergoing cardiac surgery. Two large randomized controlled trials (RCTs), however, showed no advantages of levosimendan.

Methods: We performed a systematic review and meta-analysis (MEDLINE and Embase from inception until March 30, 2017), investigating whether levosimendan offers advantages compared with placebo in high-risk cardiac surgery patients, as defined by preoperative left ventricular ejection fraction (LVEF) ≤ 35% and/or low cardiac output syndrome (LCOS). The primary outcomes were mortality at longest follow-up and need for postoperative renal replacement therapy (RRT). Secondary postoperative outcomes investigated included myocardial injury, supraventricular arrhythmias, development of LCOS, acute kidney injury (AKI), duration of mechanical ventilation, intensive care unit and hospital lengths of stay, and incidence of hypotension during drug infusion.

Results: Six RCTs were included in the meta-analysis, five of which investigated only patients with LVEF ≤ 35% and one of which included predominantly patients with LCOS. Mortality was similar overall (OR 0.64 [0.37, 1.11], p = 0.11) but lower in the subgroup with LVEF < 35% (OR 0.51 [0.32, 0.82], p = 0.005). Need for RRT was reduced by levosimendan both overall (OR 0.63 [0.42, 0.94], p = 0.02) and in patients with LVEF < 35% (OR 0.55 [0.31, 0.97], p = 0.04). Among secondary outcomes, we found lower postoperative LCOS in patients with LVEF < 35% receiving levosimendan (OR 0.49 [0.27, 0.89], p = 0.02), lower overall AKI (OR 0.62 [0.42, 0.92], p = 0.02), and a trend toward lower mechanical support, both overall (p = 0.07) and in patients with LVEF < 35% (p = 0.05).

Conclusions: Levosimendan reduces mortality in patients with preoperative severely reduced LVEF but does not affect overall mortality. Levosimendan reduces the need for RRT after high-risk cardiac surgery.

Keywords: Ejection fraction; Intensive care; Mortality; Renal replacement therapy.

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Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Forest plot depicting analysis of the risk of mortality at longest follow-up in patients treated with levosimendan vs placebo. LVEF Left ventricular ejection fraction, LCOS Low cardiac output syndrome, M-H Mantel-Haenszel
Fig. 2
Fig. 2
Forest plot depicting analysis of the risk for postoperative renal replacement therapy in patients treated with levosimendan vs placebo. LVEF Left ventricular ejection fraction, LCOS Low cardiac output syndrome, M-H Mantel-Haenszel
Fig. 3
Fig. 3
Forest plot depicting analysis of the risk for postoperative low cardiac output syndrome in patients treated with levosimendan vs placebo and with low preoperative left ventricular ejection fraction. M-H Mantel-Haenszel

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