Objective

The aim was to test the hypothesis that preoperative infusion of levosimendan would decrease patients’ cardiac biomarker profiles during the immediate postoperative stage (troponin I and B-type natriuretic peptide levels) more efficiently than placebo after cardiopulmonary bypass.

Methods

In a randomised, placebo-controlled, double-blinded study, 30 paediatric patients were scheduled for congenital heart disease surgery. 15 patients (50%) received prophylactic levosimendan and 15 patients (50%) received placebo from 12 h before cardiopulmonary bypass to 24 h after surgery.

Results

Troponin I levels were higher in the placebo group at 0, 12, and 24 h after cardiopulmonary bypass, although the mean differences between the study groups and the 95% confidence intervals (CIs) for troponin I levels did not present statistically significant differences at any of the three time points considered (mean differences [95% CIs] − 3.32 pg/ml [− 19.34 to 12.70], − 2.42 pg/ml [− 19.78 to 13.95], and − 79.94 pg/ml [− 266.99 to 16.39] at 0, 12, and 24 h, respectively). A similar lack of statistically significant difference was observed for B-type natriuretic peptide (mean differences [95% CIs] 36.86 pg/dl [− 134.16 to 225.64], − 350.79 pg/dl [− 1459.67 to 557.45], and − 310.35 pg/dl [− 1505.76 to 509.82]). Lactic acid levels were significantly lower with levosimendan; the mean differences between the study groups and the 95% CIs for lactate levels present statistically significant differences at 0 h (− 1.52 mmol/l [− 3.19 to − 0.25]) and 12 h (− 1.20 mmol/l [− 2.53 to − 0.10]) after cardiopulmonary bypass. Oxygen delivery (DO₂) was significantly higher at 12 h and 24 h after surgery (mean difference [95% CI] 627.70 ml/min/m² [122.34–1162.67] and 832.35 ml/min/m² [58.15 to 1651.38], respectively).

Conclusions

Levosimendan does not significantly improve patients’ postoperative troponin I and B-type natriuretic peptide profiles during the immediate postoperative stage in comparison with placebo, although both were numerically higher with placebo. Levosimendan, however, significantly reduced lactic acid levels and improved patients’ DO₂ profiles. These results highlight the importance of this new drug and its possible benefit with regard to myocardial injury; however, evaluation in larger, adequately powered trials is needed to determine the efficacy of levosimendan.

Trial registry number: EudraCT 2012-005310-19.

中文翻译：

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术前输注左西孟旦对小儿心脏手术后心肌损伤生物标志物和血流动力学的影响：随机对照试验

 客观的

目的是检验以下假设：术前输注左西孟旦会比体外循环后的安慰剂更有效地降低术后即刻阶段患者的心脏生物标志物谱（肌钙蛋白 I 和 B 型利尿钠肽水平）。

 方法

在一项随机、安慰剂对照、双盲研究中，30 名儿童患者被安排接受先天性心脏病手术。从体外循环前 12 小时到手术后 24 小时，15 名患者 (50%) 接受预防性左西孟旦治疗，15 名患者 (50%) 接受安慰剂治疗。

 结果

体外循环后 0、12 和 24 小时，安慰剂组的肌钙蛋白 I 水平较高，但研究组之间的平均差异和肌钙蛋白 I 水平的 95% 置信区间 (CI) 在任何时间点均不存在统计学显着差异。考虑的三个时间点（平均差[95% CI] − 3.32 pg/ml [− 19.34 至 12.70]、− 2.42 pg/ml [− 19.78 至 13.95] 和 − 79.94 pg/ml [− 266.99 至 16.39]分别在 0、12 和 24 小时）。 B 型利钠肽也观察到类似的缺乏统计学显着性差异（平均差异 [95% CI] 36.86 pg/dl [− 134.16 至 225.64]、− 350.79 pg/dl [− 1459.67 至 557.45] 和 − 310.35 pg /dl [− 1505.76 至 509.82]）。左西孟旦的乳酸水平显着降低；研究组之间的平均差异和乳酸水平的 95% CI 在 0 小时 (− 1.52 mmol/l [− 3.19 至 − 0.25]) 和 12 小时 (− 1.20 mmol/l [− 2.53 至 −) 时呈现统计显着差异0.10]）体外循环后。术后 12 小时和 24 小时的氧气输送量 (DO ₂ ) 显着较高（平均差 [95% CI] 627.70 ml/min/m ² [122.34–1162.67] 和 832.35 ml/min/m ² [58.15 至 1651.38] ， 分别）。

 结论

与安慰剂相比，左西孟旦在术后即刻阶段并未显着改善患者的术后肌钙蛋白 I 和 B 型利尿钠肽谱，尽管安慰剂的数值较高。然而，左西孟旦显着降低了乳酸水平并改善了患者的 DO ₂分布。这些结果强调了这种新药的重要性及其对心肌损伤的可能益处；然而，需要进行更大规模、更有力的试验评估，以确定左西孟旦的疗效。

试验注册号：EudraCT 2012-005310-19。