Zhang Shihai, Wang Shouyong, Li Qing, Yao Shanglong, Zeng Bangxiong, Ziegelstein Roy C, Hu Qinghua
Department of Anaesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Lancet. 2005;366(9485):556-62. doi: 10.1016/S0140-6736(05)67099-7.
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.
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.
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.
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.
毛细血管渗漏综合征是体外循环（CPB）后一种危及生命的并发症，在全球儿童中的发生率约为4%-37%。基于先前的研究结果，我们开展了一项随机对照研究，以探讨用富含补体成分4的C4A同种型的血浆进行预充对C4A缺乏儿童毛细血管渗漏综合征发生率的影响。
在中国武汉的一家医院，我们将116名缺乏补体成分C4A的新生儿、婴儿和儿童随机分为两组，分别接受不含C4A或富含C4A的血浆预充（每组58例，20 mL/kg）。主要结局是毛细血管渗漏综合征，定义为伊文思蓝染料从血浆中的跨血管逸出率增加。在CPB前和CPB后4小时测量活化补体成分C4和C3、炎性介质白细胞介素6、白细胞介素8、肿瘤坏死因子（TNF）α、血浆蛋白浓度以及PaO2/F(I)O2比值（动脉血氧分压与吸入气中氧分数的比值）。分析采用意向性分析。
接受富含C4A血浆预充的3例（5%）患者发生了毛细血管渗漏综合征，而接受不含C4A血浆预充的有56例（97%）（p<0.0001）。CPB后4小时，不含C4A组的活化C4、白细胞介素6、白细胞介素8和TNFα浓度较高，而PaO2/F(I)O2比值和血浆蛋白浓度显著低于富含C4A组的变化。两组中活化C3的升高程度相同。活化C4与白细胞介素6、白细胞介素8和TNFα浓度、PaO2/F(I)O2比值以及CPB后4小时伊文思蓝染料的逸出率显著相关。不含C4A组的2例患者在CPB后第3天死于呼吸和肾衰竭。
在C4A缺乏的儿科患者中，富含C4A的血浆预充通过阻止活化C4的增加并减轻CPB后的全身炎症反应，降低了CPB相关毛细血管渗漏综合征的发生率。
