The Effect of Methylprednisolone on Plasma Concentrations of Neutrophil Gelatinase–Associated Lipocalin in Pediatric Heart Surgery*

The Effect of Methylprednisolone on Plasma Concentrations of Neutrophil Gelatinase–Associated Lipocalin in Pediatric Heart Surgery*
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小儿心脏手术中甲基强的松龙对中性粒细胞明胶酶相关脂质运载蛋白血浆浓度的影响*

DOI:
10.1097/pcc.0000000000000573
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发表时间:
2016
影响因子:
4.1
通讯作者:
T. Jahnukainen
T. Jahnukainen
中科院分区:
医学2区
文献类型:
--
作者:
E. Pesonen;P. Suominen;J. Keski;I. Mattila;P. Rautiainen;T. Jahnukainen

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目的:血浆中性粒细胞明胶酶相关脂钙蛋白是小儿心脏手术中应用的肾脏损伤标志物。中性粒细胞明胶酶相关的Lipocalin也是中性粒细胞特定颗粒的组成部分。皮质类固醇在儿童心脏手术中被广泛使用。甲基强的松龙抑制中性粒细胞特异性颗粒的脱颗粒。儿科心脏手术中性粒细胞明胶酶相关脂蛋白的研究没有考虑皮质类固醇的使用。我们研究了在小儿心脏手术中全身应用甲基强的松龙对血浆中性粒细胞明胶酶相关脂蛋白浓度的影响。设计:两个独立的双盲随机试验。环境:一所大学附属医院的PICU。患者:40例接受心内直视手术的新生儿和45例接受室间隔和房室间隔缺损矫正术的儿童。干预:第一个试验(新生儿试验),40例接受心内直视手术的新生儿接受30 mg/kg静脉注射甲基强的松龙(n=20)或安慰剂(n=20)。第二个试验(室间隔缺损试验),45例接受室间隔或房室间隔缺损矫正术的儿童接受以下一种治疗:麻醉诱导后给予甲基强的松龙30 mg/kg(n=15),在体外循环原液中给予甲基强的松龙30 mg/kg(n=15),或安慰剂(n=15)。测量方法和主要结果:两组患者均测定了中性粒细胞、明胶酶相关脂蛋白和肌酐。仅在室间隔缺损试验中,乳铁蛋白水平被测量为中性粒细胞特异性颗粒的标志。在两组试验中,肌酐水平均无差异。术前,中性粒细胞明胶酶相关的Lpocalin在两个试验的研究组之间没有差别。在新生儿试验中,术前应用甲基强的松龙使术后6小时中性粒细胞明胶酶相关脂蛋白降低了41%(p=0.002)。室间隔缺损术前应用甲基强的松龙,术后6小时中性粒细胞明胶酶相关脂蛋白减少47%(p=0.010),乳铁蛋白减少52%(p=0.013)。室间隔缺损试验中乳铁蛋白水平与中性粒细胞明胶酶相关脂蛋白相关(R=0.492;p=0.001)相关(R=0.492;p=0.001),停用体外循环后(R=0.471;p=0.001)。结论:术前给予甲基强的松龙可显著降低血浆中性粒细胞明胶酶相关脂钙蛋白水平。中性粒细胞明胶酶相关的Lipocalin似乎在很大程度上来源于激活的中性粒细胞。在小儿心脏手术中,术前甲基强的松龙是解释血浆中性粒细胞明胶酶相关脂结合蛋白水平为肾损伤标志物时的一个混杂因素。
Objectives: Plasma neutrophil gelatinase–associated lipocalin is a kidney injury marker used in pediatric heart surgery. Neutrophil gelatinase–associated lipocalin is also a constituent of specific granules of neutrophils. Corticosteroids are widely used in pediatric heart surgery. Methylprednisolone inhibits degranulation of neutrophil-specific granules. Use of corticosteroids has not been taken into account in studies of neutrophil gelatinase–associated lipocalin in pediatric heart surgery. We studied the influence of systemically administered methylprednisolone on plasma neutrophil gelatinase–associated lipocalin concentrations in pediatric heart surgery. Design: Two separate double-blinded randomized trials. Setting: PICU at a university-affiliated hospital. Patients: Forty neonates undergoing open-heart surgery and 45 children undergoing ventricular and atrioventricular septal defect correction. Interventions: First trial (neonate trial), 40 neonates undergoing open-heart surgery received either 30 mg/kg IV methylprednisolone (n = 20) or placebo (n = 20). Second trial (ventricular septal defect trial), 45 children undergoing ventricular or atrioventricular septal defect correction received one of the following: 30 mg/kg of methylprednisolone IV after anesthesia induction (n = 15), 30 mg/kg methylprednisolone in the cardiopulmonary bypass prime solution (n = 15), or placebo (n = 15). Measurements and Main Results: Plasma neutrophil gelatinase–associated lipocalin and creatinine were measured in both series. Lactoferrin levels were measured as a marker of neutrophil-specific granules in the ventricular septal defect trial only. No differences in creatinine levels occurred between the groups of either trial. Preoperative, neutrophil gelatinase–associated lipocalin did not differ between the study groups of either trial. Preoperatively administered methylprednisolone in the neonate trial reduced neutrophil gelatinase–associated lipocalin by 41% at 6 hours postoperatively (p = 0.002). Preoperatively administered methylprednisolone in the ventricular septal defect trial reduced neutrophil gelatinase–associated lipocalin by 47% (p = 0.010) and lactoferrin by 52% (p = 0.013) 6 hours postoperatively. Lactoferrin levels in the ventricular septal defect trial correlated with neutrophil gelatinase–associated lipocalin (R = 0.492; p = 0.001) preoperatively and after weaning from cardiopulmonary bypass (R = 0.471; p = 0.001). Conclusions: Preoperatively administered methylprednisolone profoundly decreases plasma neutrophil gelatinase–associated lipocalin levels. Neutrophil gelatinase–associated lipocalin seems to originate to a significant extent from activated neutrophils. Preoperative methylprednisolone is a confounding factor when interpreting plasma neutrophil gelatinase–associated lipocalin levels as a kidney injury marker in pediatric heart surgery.
DOI: 10.1681/asn.2010111163
发表时间: 2011-09-01
影响因子: 13.6
作者:
Parikh, Chirag R.;Devarajan, Prasad;Krawczeski, Catherine D.
通讯作者: Krawczeski, Catherine D.
DOI: 10.1097/01.asn.0000088027.54400.c6
发表时间: 2003-10-01
影响因子: 13.6
作者:
Mishra, J;Ma, Q;Devarajan, P
通讯作者: Devarajan, P
DOI: 10.1016/j.jpeds.2010.12.057
发表时间: 2011-06-01
影响因子: 5.1
作者:
Krawczeski, Catherine D.;Woo, Jessica G.;Devarajan, Prasad
通讯作者: Devarajan, Prasad