Department of Neonatology, La Paz University Hospital, Madrid, Spain.
Pediatr Res. 2013 Jan;73(1):95-103. doi: 10.1038/pr.2012.154. Epub 2012 Nov 8.
Inodilators are routinely used in cardiovascular surgery with cardiopulmonary bypass (CPB). Information regarding safety and tolerability of the novel molecule, levosimendan (LEVO), in newborns is anecdotal; no pharmacokinetic data in this population are available.
This was a phase I, randomized, and blinded study. Neonates undergoing surgical repair for congenital heart defects received stepwise dose increases of milrinone (MR; 0.5-1 μg/kg/min, n = 9) or LEVO (0.1-0.2 μg/kg/min, n = 11) as an i.v. continuous infusion, starting before CPB. Infants had continuous, time-locked, physiological, and near-infrared spectroscopy (NIRS) (cerebral and peripheral) recordings during the first 24 h, and at 48 and 96 h postsurgery. Serial biochemistry and pharmacokinetic studies were performed.
During the first 24 h postsurgery, patients showed time-related, group-independent increased cerebral tissue oxygenation and decreased diastolic blood pressure; in addition, group-dependent differences in heart rate and peripheral perfusion were found. Early postsurgery, MR-treated infants showed lower pH, higher glycemia, and higher inotrope score. The groups differed in cerebral NIRS-derived variables from 24 to 96 h. Study drug withdrawal at 96 h was more frequent with LEVO. LEVO intermediate metabolites were detected in plasma at day 14 after surgery.
LEVO is well tolerated in critically ill neonates. LEVO may have advantages over MR in terms of the dosing regimen.
在体外循环（CPB）心血管手术中，经常使用正性肌力药物。新型药物左西孟旦（LEVO）在新生儿中的安全性和耐受性信息仅为经验性报道；该人群中尚无药代动力学数据。
这是一项 I 期、随机、双盲研究。接受先天性心脏缺陷手术修复的新生儿在 CPB 前接受米力农（MR；0.5-1μg/kg/min，n=9）或 LEVO（0.1-0.2μg/kg/min，n=11）的逐步剂量递增静脉持续输注。婴儿在术后的前 24 小时以及 48 小时和 96 小时进行连续、定时锁定的生理和近红外光谱（NIRS）（脑和外周）记录。进行了系列生化和药代动力学研究。
术后 24 小时内，患者表现出与时间相关的、与组无关的脑氧合增加和舒张压低；此外，还发现了与组相关的心率和外周灌注差异。术后早期，MR 治疗的婴儿表现出更低的 pH 值、更高的血糖和更高的正性肌力评分。两组在术后 24 小时至 96 小时之间的脑 NIRS 衍生变量上存在差异。术后第 96 小时，LEVO 组停药更频繁。术后第 14 天在血浆中检测到 LEVO 的中间代谢物。
LEVO 在危重新生儿中耐受良好。LEVO 在给药方案方面可能优于 MR。
