Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: a prospective randomized controlled trial.

BACKGROUND: The administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts. METHODS: This was a single-center, double-blind, randomized, placebo-controlled trial. Patients ≤ 48 months old were enrolled between July 2018 and April 2019 and were randomly assigned to groups that received either placebo or levosimendan infusions for 48 h post-surgery, along with all other standard methods of care. LCOS incidence was the primary outcome of this study. RESULTS: A total of 187 patients were enrolled, of whom 94 and 93 received levosimendan and placebo, respectively. LCOS incidence did not differ significantly between the levosimendan and placebo groups (10 [10.6%] versus 18 [19.4%] patients, respectively; 95% confidence interval [CI] 0.19-1.13; p = 0.090) nor did 90-day mortality (3 [3.2%] versus 4 [4.3%] patients, CI 0.14-3.69, p = 0.693), duration of mechanical ventilation (median, 47.5 h and 39.5 h, respectively; p = 0.532), ICU stay (median, 114.5 h and 118 h, respectively; p = 0.442), and hospital stay (median, 20 days and 20 days, respectively; p = 0.806). The incidence of hypotension and cardiac arrhythmia did not differ significantly between the groups. Levels of levosimendan fell rapidly without any plateau in plasma concentrations during infusion. A multiple logistic regression indicated that randomization to the levosimendan group was a predictor of LCOS. CONCLUSIONS: Prophylactic levosimendan administration was safe in pediatric patients and had some benefit to postoperative hemodynamic parameters, but failed to provide significant benefit with respect to LCOS or 90-day mortality relative to placebo. TRIAL REGISTRATION: Name of the registry: Safety evaluation and therapeutic effect of levosimendan on the low cardiac output syndrome in patients after cardiopulmonary bypass. TRIAL REGISTRATION NUMBER: ChiCTR1800016594. Date of registration: 11 June 2018. URL of trial registry record: http://www.chictr.org.cn/index.aspx.

Comparison of Levosimendan and Milrinone for ECLS Weaning in Patients After Cardiac Surgery-A Retrospective Before-and-After Study.

OBJECTIVES: Pharmacodynamics suggests that levosimendan might be a valuable inotrope for weaning from extracorporeal life support (ECLS). As there is a paucity of evidence regarding the effectiveness and safety of such an approach, the aim was to report the authors' experiences in ECLS weaning before and after the implementation of levosimendan in clinical practice. DESIGN: Retrospective before-and-after study. SETTING: Cardiac intensive care unit of a university hospital. PARTICIPANTS: A total of 64 patients under ECLS for postcardiotomy cardiac failure, who underwent an ECLS weaning trial. INTERVENTION: Group comparisons between patients treated with levosimendan and patients treated with milrinone were made with the Mann-Whitney U test or the Pearson chi-squared test. Results are given as median (interquartile range) or numbers (percentages). MEASUREMENTS AND MAIN RESULTS: Of 64 patients, 26 (41%) received levosimendan. Successful ECLS weaning was achieved in 24 (92%) and 30 patients (79%) in the levosimendan and milrinone group, respectively (p = 0.18). In the levosimendan group, fewer patients had an intra-aortic balloon pump for weaning (2 [7.7%] v 15 [40%], p = 0.008). The support with norepinephrine was similar in the levosimendan and milrinone groups at the time of ECLS removal (0.06 [0.01-0.11] v 0.07 [0.01-0.16] µg/kg/min, p = 0.64) and 24 hours later (0.06 [0.04-0.09] v 0.04 [0.00-0.09] µg/kg/min, p = 0.15). Twenty-eight days (9/26 (35%) v 14/35 (40%), p = 0.28) and 180 days (13/26 [50%] v 15/34 [44%], p = 0.80) mortalities after ECLS removal were similar in the levosimendan and the milrinone groups. CONCLUSION: Levosimendan enabled ECLS weaning without increasing norepinephrine requirements when compared to a control group receiving milrinone.

Levosimendan enhances memory through antioxidant effect in rat model: behavioral and molecular study.

Impairment of learning and memory has been associated with accumulation of reactive oxygen species in the body. It has also been found that antioxidants enhance learning and memory. Levosimendan is a cardiac inotropic and vasodilator agent that has pleotropic effects including antioxidant, anti-inflammatory, and smooth muscle vasodilatory actions. In this study, we investigated the effect of levosimendan on learning and memory in rats. Levosimendan (12 µg/kg, intraperitoneally) or vehicle was administered once a week for 8 weeks. The radial arm water maze was used to assess spatial learning and memory. In addition, hippocampus levels of antioxidant biomarkers/enzyme - reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase, superoxide dismutase, catalase, and thiobarbituric acid reactive substance - were assessed. Levosimendan significantly enhanced short-term (30 min) and long-term (5 h) memory. Levosimendan also significantly increased levels of glutathione peroxidase and GSH and decreased thiobarbituric acid reactive substance. There were no significant effects on the level of other oxidative stress biomarkers. In conclusion, levosimendan enhanced short-term and long-term memory by potentiating antioxidant defense mechanism in the hippocampus.