Abstract: We included five randomised controlled trials with a total of 212 participants in the analyses. All included participants were under five years of age. Using GRADE, we assessed there was low-quality evidence for all analysed outcomes. We assessed high risk of performance and detection bias for two studies due to their unblinded setting. Levosimendan showed no clear effect on risk of mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.12 to 1.82; participants = 123; studies = 3) and no clear effect on low cardiac output syndrome (RR 0.64, 95% CI 0.39 to 1.04; participants = 83; studies = 2) compared to standard treatments. Data on time-to-death were not available from any of the included studies. There was no conclusive evidence on the effect of levosimendan on the secondary outcomes. The length of intensive care unit stays (mean difference (MD) 0.33 days, 95% CI -1.16 to 1.82; participants = 188; studies = 4), length of hospital stays (MD 0.26 days, 95% CI -3.50 to 4.03; participants = 75; studies = 2), duration of mechanical ventilation (MD -0.04 days, 95% CI -0.08 to 0.00; participants = 208; studies = 5), and the risk of mechanical circulatory support or cardiac transplantation (RR 1.49, 95% CI 0.19 to 11.37; participants = 60; studies = 2) did not clearly differ between the groups. Published data about adverse effects of levosimendan were limited. A meta-analysis of hypotension, one of the most feared side effects of levosimendan, was not feasible because of the heterogeneous expression of blood pressure values. The current level of evidence is insufficient to judge whether prophylactic levosimendan prevents low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. So far, no significant differences have been detected between levosimendan and standard inotrope treatments in this setting. The authors evaluated the quality of evidence as low, using the GRADE approach. Reasons for downgrading were serious risk of bias (performance and detection bias due to unblinded setting of two RCTs), serious risk of inconsistency, and serious to very serious risk of imprecision (small number of included patients, low event rates).

Plain-language summary: We identified five studies that had a total of 212 patients. All patients were under five years of age. The patients were given levosimendan during or immediately after heart surgery for a duration of 20 to 72 hours. They were monitored for 20 hours to six days. We asked all of the study authors for additional information about their trials. All but one author responded. The evidence is current to June 2016. We found low-quality evidence for all outcomes. This was mainly due to the small number of included patients (high imprecision of results). Thus, all results of the meta-analysis must be viewed with caution. The available data revealed no clear difference between levosimendan and conventional medication in preventing reduced heart function and death after heart surgery in the studied population. We also found no clear difference in the length of stay in the intensive care unit. The available data did not allow us to judge whether one of the treatment arms was superior to the other for three secondary outcomes: length of hospital stay, time on mechanical ventilation, need to implant circulatory support devices or the need for cardiac transplantation. Overall, few side effects were reported in any of the groups. We were unable to pool data to generate useful information about the safety of levosimendan.