Abstract：
BACKGROUND: Capillary leak syndrome is a life-threatening complication after cardiopulmonary bypass (CPB), with an incidence of about 4-37% in children worldwide. On the basis of previous results, we undertook a randomised controlled study to investigate the priming with plasma rich in the C4A isotype of complement component 4 on the incidence of capillary leak syndrome in children with C4A deficiency.
METHODS: In a hospital in Wuhan, China, we randomly assigned 116 neonates, infants, and children lacking complement component C4A to receive C4A-free or C4A-rich plasma priming (n=58 each, 20 mL/kg). The primary outcome was capillary leak syndrome, identified as an increased transvascular escape rate of Evans blue dye from plasma. Concentrations of activated complement components C4 and C3, inflammatory mediators interleukin 6, interleukin 8, tumour necrosis factor (TNF) alpha, plasma protein, and PaO2/F(I)O2 ratios (ratio of the partial arterial pressure of oxygen to the fractional concentration of oxygen in inspired air) were measured before and 4 h after CPB. Analysis was by intention to treat.
RESULTS: Three (5%) patients given C4A-rich plasma priming had capillary leak syndrome compared with 56 (97%) given C4A-free plasma (p<0.0001). At 4 h after CPB, activated C4, interleukin 6, interleukin 8, and TNFalpha concentrations were higher, whereas PaO2/F(I)O2 ratios and plasma protein concentrations were significantly lower in the C4A-free group than changes in the C4A-rich group. Activated C3 rose equally in both groups. Activated C4 significantly correlated with interleukin 6, interleukin 8, and TNFalpha concentrations; PaO2/F(I)O2 ratios; and the escape rate of Evans blue dye at 4 h after CPB. Two patients in the C4A-free group died of respiratory and renal failure on day 3 after CPB.
CONCLUSIONS: In paediatric patients with C4A deficiency, C4A-rich plasma priming reduces the incidence of CPB-related capillary leak syndrome by blocking the activated C4 increase and attenuating the systemic inflammatory response after CPB.
METHODS: In a hospital in Wuhan, China, we randomly assigned 116 neonates, infants, and children lacking complement component C4A to receive C4A-free or C4A-rich plasma priming (n=58 each, 20 mL/kg). The primary outcome was capillary leak syndrome, identified as an increased transvascular escape rate of Evans blue dye from plasma. Concentrations of activated complement components C4 and C3, inflammatory mediators interleukin 6, interleukin 8, tumour necrosis factor (TNF) alpha, plasma protein, and PaO2/F(I)O2 ratios (ratio of the partial arterial pressure of oxygen to the fractional concentration of oxygen in inspired air) were measured before and 4 h after CPB. Analysis was by intention to treat.
RESULTS: Three (5%) patients given C4A-rich plasma priming had capillary leak syndrome compared with 56 (97%) given C4A-free plasma (p<0.0001). At 4 h after CPB, activated C4, interleukin 6, interleukin 8, and TNFalpha concentrations were higher, whereas PaO2/F(I)O2 ratios and plasma protein concentrations were significantly lower in the C4A-free group than changes in the C4A-rich group. Activated C3 rose equally in both groups. Activated C4 significantly correlated with interleukin 6, interleukin 8, and TNFalpha concentrations; PaO2/F(I)O2 ratios; and the escape rate of Evans blue dye at 4 h after CPB. Two patients in the C4A-free group died of respiratory and renal failure on day 3 after CPB.
CONCLUSIONS: In paediatric patients with C4A deficiency, C4A-rich plasma priming reduces the incidence of CPB-related capillary leak syndrome by blocking the activated C4 increase and attenuating the systemic inflammatory response after CPB.
摘要：
背景：毛细血管渗漏综合征是体外循环（CPB）后危及生命的并发症，全世界儿童的发病率约为4-37%。在以往成果的基础上,我们进行了一项随机对照研究,以研究富含C4A同种型补体成分4的血浆引发对C4A缺乏症儿童毛细血管渗漏综合征发生率的影响.
方法：在武汉某医院，中国,我们随机分配了116名新生儿，婴儿,和缺乏补体成分C4A的儿童接受无C4A或富含C4A的血浆引发（每个n=58，20mL/kg)。主要结果是毛细血管渗漏综合征，确定为伊文思蓝染料从血浆中的经血管逃逸率增加。激活的补体成分C4和C3，炎症介质白介素6，白介素8，肿瘤坏死因子（TNF）α的浓度，血浆蛋白，在CPB之前和之后4小时测量PaO2/F（I）O2比率（氧气的动脉分压与吸入空气中氧气的分数浓度之比）。分析是有意治疗。
结果：3例（5%）给予富含C4A的血浆预激患者出现毛细血管渗漏综合征，而56例（97%）给予不含C4A的血浆（p<0.0001）。CPB后4小时，活化C4、白细胞介素6、白细胞介素8和TNFα浓度较高，而无C4A组的PaO2/F(I)O2比值和血浆蛋白浓度显著低于富含C4A组的变化。激活的C3在两组中上升相等。活化的C4与白细胞介素6，白细胞介素8和TNFα浓度显着相关；PaO2/F（I）O2比率；以及CPB后4小时伊文思蓝染料的逃逸率。无C4A组的两名患者在CPB后第3天死于呼吸和肾衰竭。
结论：在C4A缺乏症的儿科患者中，富含C4A的血浆引发通过阻断激活的C4增加和减轻CPB后的全身炎症反应来降低CPB相关毛细血管渗漏综合征的发生率。
方法：在武汉某医院，中国,我们随机分配了116名新生儿，婴儿,和缺乏补体成分C4A的儿童接受无C4A或富含C4A的血浆引发（每个n=58，20mL/kg)。主要结果是毛细血管渗漏综合征，确定为伊文思蓝染料从血浆中的经血管逃逸率增加。激活的补体成分C4和C3，炎症介质白介素6，白介素8，肿瘤坏死因子（TNF）α的浓度，血浆蛋白，在CPB之前和之后4小时测量PaO2/F（I）O2比率（氧气的动脉分压与吸入空气中氧气的分数浓度之比）。分析是有意治疗。
结果：3例（5%）给予富含C4A的血浆预激患者出现毛细血管渗漏综合征，而56例（97%）给予不含C4A的血浆（p<0.0001）。CPB后4小时，活化C4、白细胞介素6、白细胞介素8和TNFα浓度较高，而无C4A组的PaO2/F(I)O2比值和血浆蛋白浓度显著低于富含C4A组的变化。激活的C3在两组中上升相等。活化的C4与白细胞介素6，白细胞介素8和TNFα浓度显着相关；PaO2/F（I）O2比率；以及CPB后4小时伊文思蓝染料的逃逸率。无C4A组的两名患者在CPB后第3天死于呼吸和肾衰竭。
结论：在C4A缺乏症的儿科患者中，富含C4A的血浆引发通过阻断激活的C4增加和减轻CPB后的全身炎症反应来降低CPB相关毛细血管渗漏综合征的发生率。
