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

Abstract

BackgroundThe 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.MethodsThis 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.ResultsA 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.ConclusionsProphylactic 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 registrationName 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

Effect of Prophylactic Levosimendan on All-Cause Mortality in Pediatric Patients Undergoing Cardiac Surgery—An Updated Systematic Review and Meta-Analysis

“…Thirty-six literatures were excluded because they did not meet the eligible criteria by browsing the titles and abstracts, and 16 literatures were removed by browsing the full text. Eventually, 7 trials including 436 patients were indentified through our search strategy [ Figure 1 ; ( 24 – 30 )].…”

“…The basic information of all included trials is shown in Table 1 . Four trials ( 24 , 26 – 28 ) were conducted in European countries, and 3 trials ( 25 , 29 , 30 ) in Asian countries. All patients included in the 7 articles were under 5 years old.…”

“…One trial ( 26 ) selected the pediatric patients younger than 1 year, and 2 trials ( 27 , 28 ) younger than 30 d. Six literatures ( 24 – 28 , 30 ) including 396 patients were RCTs, and 1 literature ( 29 ) including 40 patients was CCT. There were 3 articles ( 24 , 26 , 27 ) comparing levosimendan with milrinone, 1 article ( 25 ) with dobutamine, 1 article ( 30 ) with placebo, and 2 articles ( 28 , 29 ) with the standard inotropic management. The loading dose was administrated in 1 trial ( 25 ).…”

“…Three trials demonstrated the incidence of LCOS (27,28,30). The pooled result showed striking difference in LCOS incidence [RR = 0.60, 95% CI (0.40, 0.91), I 2 = 0, P for effect = 0.016] (Figure 7).…”

Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: the jury is still out

“…The study by Wang et al on levosimendan used in prophylaxis of low cardiac output syndrome (LCOS) post-pediatric cardiac surgery is the first study comparing levosimendan versus placebo. The authors did not show an impact on mortality or on the occurrence of LCOS [1]. However, it is very interesting to see that in the multivariate regression analysis, levosimendan had an impact on the onset of LCOS (OR 0.38 and p = 0.037).…”