细胞外组蛋白在先天性心脏病围手术期的变化及临床应用

目的 研究先天性心脏病患儿首次纠治术围手术期细胞外组蛋白的变化趋势,及其预测临床预后的价值.方法 分别收集32例紫绀型先天性心脏病患儿在术前(T0)、术后即刻(T1)、4h(T2)、24 h(T3)、48 h(T4)和72 h(T5)的外周血,检测血清细胞外组蛋白及血清氨基末端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP).将细胞外组蛋白与NT-proBNP及术后临床参数作相关性分析,并用受试者工作特征曲线(ROC曲线)对细胞外组蛋白的预后价值进行评估.结果 细胞外组蛋白术后开始升高,在T1时达到峰值(0.762±0.287) μg/ml,在T4时(0.271±0.145)μg/ml回降接近T0时(0.194±0.098) μg/ml水平.NT-proBNP于T3时达到峰值(7 725.0±3 502.3)pg/ml,T5时水平(5 123.0±3 211.8) pg/ml仍显著高于T0时(478.4±206.1) pg/ml.线性回归分析示,T1时细胞外组蛋白与T3时NT-proBNP(r=0.772,P＜0.01)、体外循环时间(r=0.882,P＜0.01)、主动脉阻断时间(r=0.795,P＜0.01)、术后机械通气时间(r=0.607,P＜0.01)、重症监护室(ICU)时间(r=0.602,P＜0.01)之间均有统计学相关性.ROC曲线分析示T1时细胞外组蛋白水平对术后48 h内正性肌力药物评分(VIS)＞10的预测敏感度为61.5％,特异度为84.2％,界值为0.786 μg/ml,曲线下面积(area under curve,AUC)为0.729;对术后ICU时间＞5d的预测敏感度为81.8％,特异度为76.2％,界值为0.837 μg/ml,AUC为0.814.结论 术后细胞外组蛋白较NT-proBNP更早达到峰值,且其峰值与病情严重程度相关,可作为紫绀型先天性心脏病患儿首次纠治术后的早期临床预后指标.

Perioperative changes and clinical applications of extracellular histones during pediatric cardiac surgery

Objective To explore the perioperative changes and clinical applications of extracellular histones and examine its predictive value for clinical outcomes after cardiopulmonary bypass (CPB) in children.Methods Thirty-two children of cyanotic congenital heart disease undergoing corrective procedures with CPB were prospectively enrolled.The levels of extracellular histones and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured at pre-OP (operation) (T0),post-OP hour 0 (T1),post-OP hour 4 (T2),post-OP hour 24 (T3),post-OP hour 48 (T4) and post-OP hour 72 (T5).The relationships between extracellular histones,NT-proBNP and other clinical parameters were analyzed.Results The levels of extracellular histones increased significantly post-OP,peaked at T1 (0.762 ± 0.287) μg/ml and then declined rapidly back to baseline level T0 (0.194 ± 0.098) μg/ml at T4 (0.271 ± 0.145) μg/ml.The level of NT-proBNP rose significantly post-OP and peaked at T3 (7 725.0 ± 3 502.3) pg/ml.And it stayed significantly higher at T5 (5 123.0-± 3 211.8 pg/ml) than that at T0 (478.4 ± 206.1 pg/ml).The peak level of extracellular histones was statistically correlated with peak NT-proBNP level (r =0.772,P＜0.01) as well as CPB time (r=0.882,P＜0.01),cross-clamp time (r=0.795,P＜0.01),ventilation time (r =0.607,P ＜0.01) and intensive care unit (ICU) time (r =0.602,P＜0.01).Receiver operating characteristic (ROC) curve analysis showed that peak levels of extracellular histones had predictive values for vasoactive-inotropic support (VIS) ＞ 10 post-OP 48 h with AUC =0.729 (cut-off:0.786 μg/ml;sensitivity:61.5％;specificity:84.2％) and ICU time ＞5 days with AUC =0.814 (cut-off:0.837 μg/ml;sensitivity:81.8％;specificity:76.2％).Conclusions The levels of extracellular histones peak more rapidly than that of NT-pro BNP.And peak levels of extracellular histones had statistically significant correlations with clinical parameters postoperatively.The levels of extracellular histones at post-OP hour 0 may become an early prognostic indicator for children after CPB.