Pediatric Intensive Care Unit, Hospital Universitario Virgen de las Nieves, University of Granada, Granada, Spain.
Paediatric Cardiology Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Drugs R D. 2021 Mar;21(1):79-89. doi: 10.1007/s40268-020-00332-1. Epub 2020 Dec 24.
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.
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.
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 (DO) was significantly higher at 12 h and 24 h after surgery (mean difference [95% CI] 627.70 ml/min/m [122.34-1162.67] and 832.35 ml/min/m [58.15 to 1651.38], respectively).
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' DO 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.
检验假设，即在体外循环后即刻阶段（肌钙蛋白 I 和 B 型利钠肽水平），与安慰剂相比，术前输注左西孟旦能更有效地降低患者的心脏生物标志物谱。
在一项随机、安慰剂对照、双盲研究中，30 名小儿患者被安排接受先天性心脏病手术。15 名患者（50%）从体外循环前 12 小时至手术后 24 小时预防性给予左西孟旦，15 名患者（50%）给予安慰剂。
在体外循环后 0、12 和 24 小时，安慰剂组的肌钙蛋白 I 水平较高，但两组之间的平均差异和肌钙蛋白 I 水平的 95%置信区间（CI）在任何三个考虑的时间点均无统计学意义（0 小时的平均差异[95%CI]为-3.32 pg/ml[-19.34 至 12.70]，-2.42 pg/ml[-19.78 至 13.95]，-79.94 pg/ml[-266.99 至 16.39]；12 小时的平均差异[95%CI]为 36.86 pg/dl[-134.16 至 225.64]，-350.79 pg/dl[-1459.67 至 557.45]，-310.35 pg/dl[-1505.76 至 509.82]）。B 型利钠肽也观察到类似的无统计学差异（平均差异[95%CI]为 36.86 pg/dl[-134.16 至 225.64]，-350.79 pg/dl[-1459.67 至 557.45]，-310.35 pg/dl[-1505.76 至 509.82]）。左西孟旦的乳酸水平显著降低；两组间的平均差异和乳酸水平的 95%CI 在体外循环后 0 小时（-1.52 mmol/l[-3.19 至-0.25]）和 12 小时（-1.20 mmol/l[-2.53 至-0.10]）具有统计学意义。手术后 12 小时和 24 小时，氧输送（DO）显著升高（平均差异[95%CI]分别为 627.70 ml/min/m[122.34-1162.67]和 832.35 ml/min/m[58.15 至 1651.38]）。
与安慰剂相比，左西孟旦在体外循环后即刻阶段并没有显著改善患者的肌钙蛋白 I 和 B 型利钠肽谱，但两者均为安慰剂组更高。然而，左西孟旦显著降低了乳酸水平，并改善了患者的 DO 谱。这些结果突出了这种新药的重要性及其在心肌损伤方面的潜在益处；然而，需要更大规模、足够功率的试验来确定左西孟旦的疗效。试验注册号：EudraCT 2012-005310-19。
