Hemodynamic support of a 15-year-old waiting for a heart transplant: Is there a role for levosimendan in pediatric heart failure?

Decompensated heart failure in children requires rapid and aggressive support. In refractory cases, invasive supportive care is essential to ensure cardiac output. This results in lengthy pediatric intensive care unit (PICU) stays, secondary morbidity, and high cost. Levosimendan may help palliate the pitfalls encountered with the usual treatment. It has been shown to improve hemodynamics and decrease morbidity and mortality from heart failure in adult trials and pediatric cohorts. We report the case of a 15-year-old boy with dilated cardiomyopathy and refractory ventricular dysfunction who was weaned from continuous inotropes and discharged from the PICU with levosimendan while waiting for heart transplantation.     

Utility of the neutrophil to lymphocyte ratio for predicting in-hospital mortality after levosimendan infusion in patients with acute decompensated heart failure

BackgroundThe aim of this study was to investigate the effect of a levosimendan infusion on hematological variables in patients with acute decompensated heart failure (ADHF). The predictive value of these variables for in-hospital mortality was also evaluated.MethodsA total of 553 patients (368 males; mean age, 63.4 ± 14.9 years) with acute exacerbations of advanced heart failure (ejection fraction ≤35%) and treated with either dobutamine or levosimendan were included in this retrospective analysis. The patients that received levosimendan therapy were divided into two groups according to in-hospital mortality: group 1 (21%) included patients who died during hospitalization (n = 45), while group 2 (79%) included patients with a favorable outcome (n = 174) after levosimendan infusion. Changes in several hematological variables between admission and the third day after levosimendan infusion were evaluated.ResultsThe demographic characteristics and risk factors of the two groups were similar. A comparison of changes in laboratory variables after the infusion of levosimendan revealed significant improvement only in those patients who had not died (group 2) during hospitalization. The neutrophil to lymphocyte (N/L) ratio after levosimendan infusion was an independent predictor of in-hospital mortality (odds ratio: 1.310, 95% CI: 1.158–1.483, p < 0.001). In a receiver-operating characteristic curve analysis, a value of 5.542 for the N/L ratio after levosimendan administration was identified as an effective cut-off point for predicting in-hospital mortality (area under the curve = 0.737; 95% confidence interval = 1100–1301; p < 0.001).ConclusionsLevosimendan treatment was associated with significant changes in hematological variables in patients with ADHF. A sustained higher N/L ratio after levosimendan infusion is associated with an increased risk of in-hospital mortality in patients with ADHF.     

静脉用左西孟旦与多巴酚丁胺对急性失代偿心力衰竭患者有效性和安全性的Meta分析

目的分析比较静脉用左西孟旦与多巴酚丁胺对急性失代偿心力衰竭患者的安全性和有效性。方法通过检索PubMed、EMbase、万方、中国知网等数据库,查找静脉用左西孟旦与多巴酚丁胺治疗急性失代偿心力衰竭的随机对照实验(RCT),检索时间为1990-01-01—2011-12-15。再按纳入标准进行RCT的筛选、资料提取和证据质量评价后,利用RevMan5.0软件进行Meta分析,利用漏斗图进行证据质量评价。结果共纳入7个研究,共334例患者。Meta分析显示:(1)有效性方面:在治疗前,LVEF没有差异〔SMD=-0.74,95%CI(-1.46.-0.01),P=0.05〕;在治疗后,左西孟旦组较多巴酚丁胺组的LVEF有了显著升高〔SMD=3.18,95%CI(2.40,3.96),P<0.00001〕。(2)安全性方面:左西孟旦组与多巴酚丁胺组所致不良反应差别不大〔SMD=0.59,95%CI(0.26,1.35),P=0.21〕。结论与多巴酚丁胺比较,左西孟旦能显著提高急性失代偿心力衰竭LVEF,改善患者临床症状,值得在临床推广使用,但两者在不良反应方面差别不大。由于纳入研究的样本数较少,多中心、大样本、双盲随机对照试验应进一步验证。     

Levosimendan may provide a better neurohormonal response in heart failure patients receiving beta blocker therapy — Reply

The hemodynamic effects of levosimendan have been shown to be maintained or even enhanced by beta blockers. Furthermore, levosimendan has recently been reported to represent mortality benefit in patients receiving beta blockers. However, it is not clear whether these favorable effects of levosimendan under beta blockade are also suggested by a better neurohormonal response. We evaluated neurohormonal response to levosimendan in patients receiving beta blocker in our study population on the basis of the comments of Giamouzis and colleagues on previously published article, in which both levosimendan and dobutamine were found to be very effective inotropic agents in achieving favorable neurohormonal response but levosimendan had a better and prolonged effect. The findings of recent subgroup analysis suggested that levosimendan treatment trended toward a greater reduction in NT-proBNP levels and therefore may provide a better neurohormonal response in patients receiving beta blockers as compared with those patients not receiving beta blocker.     

静脉注射左西孟坦、多巴酚丁胺对脓毒症休克患者心肌抑制影响的对照性研究

目的 通过观察血流动力学指标以及机体炎症因子的改变探讨静脉注射左西孟坦对脓毒症休克患者心肌抑制的影响.方法 总共纳入2014年3月至2015年6月于我院治疗的脓毒症休克患者94例,在相同的基础治疗基础上,随机分为接受左西孟坦治疗组(观察组)和多巴酚丁胺治疗组(对照组);分别观察两组患者入组前、治疗3天以及7天各项指标的差异.结果 观察组和对照组在患者的平均年龄、性别构成以及基础病构成方面差异无统计学意义(P＞0.05);治疗前对两组患者的APACHE Ⅱ评分、GESVI以及血清PCT、BNP、以及Lac差异无统计学意义(P＞0.05).治疗3天以后:观察组BNP水平、Lac以及cTnl水平显著低于对照组,组间对比差异有统计学意义(P＜0.05).两组间GESVI对比差异无统计学意义(P＞0.05).连续治疗6d后,指标观测结果显示:观察组的GL以及GESVI水平显著高于对照组水平,BNP水平、Lac以及cTnl水平显著低于对照组,组间对比差异有统计学意义(P＜0.05).观察组与对照组相比,机械通气时间(P＜0.05)、住院时间较短(P＜0.05),并且APACHE Ⅱ观察组也较对照组低(P＜0.05).结论 应用左西孟坦治疗脓毒症休克患者的心肌抑制,有利于改善患者的心脏舒张和收缩功能,提高氧代谢,缩短机械通气时间和ICU住院时间,减轻机制的炎症反应,值得临床的推广应用.     

左西孟旦临床应用的循证医学

左西孟旦是一种新型的钙增敏剂和KATP通道开放剂。与其他正性肌力药相比,它在不增加氧耗的情况下提高心肌收缩力,使外周血管和冠状动脉血管扩张,可以减轻心肌缺血。目前左西孟旦在临床上应用于治疗急性心力衰竭、慢性心力衰竭、缺血性心脏病、心源性和感染中毒性休克以及成人心脏手术围术期的过渡性治疗。该文总结了近期的文献中关于左西孟旦在多种临床情况下的应用。     

左西孟旦注射剂在中国健康志愿者体内的药动学研究

目的不同剂量左西孟旦注射液在中国健康志愿者体内的药动学研究。方法12名健康志愿者,随机分为3组。于10min内分别静脉推注6,12,18μg·kg-1左西孟旦注射液后,再0.05,0.10,0.15μg·kg^-1·min^-1连续4小时静脉滴注,于给药后0.17,0.5,1,2,3,4,4.25,4.5,4.75,5,5.5,6,7,8和10小时采集肘静脉血,采用LC-MS/MS法测定左西孟旦血药浓度,用DAS2.0软件计算其药动学参数。结果3个剂量组左西孟旦主要药动学参数依次为：t1/2为1.50±0.35,1.64±0.25和1.54±0.39h;C0为9.54±3.90,15.95±7.84和28.46±10.74ng·mL^-1;AUC0-t（t=7,8）为33.63±9.34,54.39±15.34和78.36±23.74ng·mL^-1·h;AUC0-∞为36.01±8.90,56.94±15.12和81.33±24.34ng·mL^-1·h。结论静脉给予左西孟旦注射液后,C0和AUC与剂量呈良好的相关性,但与性别无关。