左西孟旦作为钙增敏剂是治疗早产儿严重心功能不全(CD)和肺动脉高压(PH)的一种有前途的创新治疗选择。但没有数据可用于分析早产儿队列中的左西孟旦.评估的设计/设置是在患有CD和PH的早产儿的大病例系列中。对2018年1月1日至2021年6月超声心动图评估中接受左西孟旦治疗和CD和/或PH的所有早产儿(胎龄(GA)<37周)的数据进行筛选分析。主要临床终点定义为对左西孟旦的超声心动图反应。最终招募早产儿(105名)进行进一步分析。早产儿(48%)被归类为极低GA新生儿(ELGANs,<28周的GA)和73%的极低出生体重婴儿(<1500g,VLBW)。主要终点达到71%,关于GA或BW没有区别。中度或重度PH的发生率从基线到随访(24小时)下降约30%,在应答者组中显著降低(p<0.001)。从基线到随访(24小时),应答组左心室功能障碍和双心室功能障碍的发生率显着降低(分别为p=0.007和p<0.001)。动脉乳酸水平从基线(4.7mmol/l)到12h(3.6mmol/l,p<0.05),和24小时(3.1mmol/l,p<0.01)。结论:左西孟旦治疗与早产儿CD和PH的改善有关。随着治疗期间平均动脉压的稳定和动脉乳酸水平的显着降低。未来的前瞻性试验是非常必要的。已知左西孟旦作为钙增敏剂和扩张剂可改善低心输出量综合征(LCOS),改善心室功能障碍,PH,无论是在儿科还是在成人人群中。没有提供与没有进行大心脏手术的危重新生儿和早产儿相关的数据。新增内容:•本研究评估了左西孟旦对血液动力学的影响,临床评分,超声心动图严重程度参数,和动脉乳酸水平首次在105名早产儿的病例系列中。左西孟旦治疗早产儿与CD和PH的快速改善有关,平均动脉压的升高,动脉乳酸水平显著下降,作为LCOS的替代标记。•这项研究可能如何影响研究,实践,或政策。由于没有关于在该人群中使用左西孟旦的数据,我们的研究结果有望激励研究界在随机对照试验(RCT)和观察对照研究中开展未来的前瞻性试验分析左西孟旦.此外,我们的结果可能会促使临床医生在早产儿重度CD和PH的情况下采用标准治疗策略,将左西孟旦作为二线治疗方案.
Levosimendan as a calcium-sensitizer is a promising innovative therapeutical option for the treatment of severe cardiac dysfunction (CD) and pulmonary hypertension (PH) in preterm infants, but no data are available analyzing levosimendan in cohorts of preterm infants. The design/setting of the evaluation is in a large
case-series of preterm infants with CD and PH. Data of all preterm infants (gestational age (GA) < 37 weeks) with levosimendan treatment and CD and/or PH in the echocardiographic assessment between 01/2018 and 06/2021 were screened for analysis. The primary clinical endpoint was defined as echocardiographic response to levosimendan. Preterm infants (105) were finally enrolled for further analysis. The preterm infants (48%) were classified as extremely low GA newborns (ELGANs, < 28 weeks of GA) and 73% as very low birth weight infants (< 1500 g, VLBW). The primary endpoint was reached in 71%, without difference regarding GA or BW. The incidence of moderate or severe PH decreased from baseline to follow-up (24 h) in about 30%, with a significant decrease in the responder group (p < 0.001). The incidence of left ventricular dysfunction and bi-ventricular dysfunction decreased significantly from baseline to follow-up (24 h) in the responder-group (p = 0.007, and p < 0.001, respectively). The arterial lactate level decreased significantly from baseline (4.7 mmol/l) to 12 h (3.6 mmol/l, p < 0.05), and 24 h (3.1 mmol/l, p < 0.01). Conclusion: Levosimendan treatment is associated with an improvement of both CD and PH in preterm infants, with a stabilization of the mean arterial pressure during the treatment and a significant decrease of arterial lactate levels. Future prospective trials are highly warranted. What is Known: • Levosimendan as a calcium-sensitizer and inodilator is known to improve the low cardiac output syndrome (LCOS), and improves ventricular dysfunction, and PH, both in pediatric as well as in adult populations. Data related to critically ill neonates without major cardiac surgery and preterm infants are not available. What is New: • This study evaluated the effect of levosimendan on hemodynamics, clinical scores, echocardiographic severity parameters, and arterial lactate levels in a
case-series of 105 preterm infants for the first time. Levosimendan treatment in preterm infants is associated with a rapid improvement of CD and PH, an increase of the mean arterial pressure, and a significant decrease in arterial lactate levels, as surrogate marker for a LCOS. • How this study might affect research, practice, or policy. As no data are available regarding the use of levosimendan in this population, our results hopefully animate the research community to conduct future prospective trails analyzing levosimendan in randomized controlled trials (RCT) and observational control studies. Additionally, our results potentially motivate clinicians to introduce levosimendan as second second-line therapy in cases of severe CD and PH in preterm infants without improvement using standard treatment strategies.