氨甲环酸对先天性心脏病患儿术后出血和抑制炎症反应的随机对照研究

Effect of tranexamic acid on postoperative hemostasis and inflammatory mediators in infants with congenital heart disease:a randomized controlled trial

目的观察先天性心脏病患儿术中应用氨甲环酸(TA)减少术后出血、输血和炎症反应的作用。方法纳入体重<10kg的先天性心脏病患儿,随机分为3组(连续TA组、分次TA组和对照组)。连续TA组:于麻醉诱导后给予TA30mg·kg-1继以16mg·kg-1·h-1维持至术毕,预充液中予TA2mg·kg-1;分次TA组:于麻醉诱导后、体外循环开始时、体外循环结束后3个时段每次予TA30mg·kg-1;对照组予生理盐水替代,给药方法和容量同连续TA组。观察并记录术后出血量、异体血制品使用情况、心脏重症监护时间、机械通气时间、术后并发症和住院病死率,观察术前、体外循环中、术后6和24hD-二聚体水平;术前、手术即刻、术后6、12和24h的血IL-8、CRP和WBC计数水平。结果 120例患儿入组,连续TA组、分次TA组和对照组各40例。3组患儿术前基线资料具可比性。①术后出血量:连续TA和分次TA组术后6h均显著低于对照组(均P<0.05),术后24h出血量和异体血制品输注量3组差异均无统计学意义(均P>0.05)。②D-二聚体水平:3组从体外循环开始至术后24h均呈持续升高趋势,连续TA和分次TA组体外循环中、术后6和24h均显著低于对照组(P<0.05),连续TA和分次TA组差异无统计学意义(P>0.05)。③IL-8水平:3组在术后即刻、12h均呈持续升高趋势,连续TA和分次TA组术后24h均出现下降趋势,并显著低于对照组(P<0.01);CRP水平:3组在术后12h均显著升高,术后24h对照组较连续TA和分次TA组显著升高(P<0.01);WBC计数:3组术后12、24h均较术前升高,差异无统计学意义。结论对体重<10kg的先天性心脏病患儿连续TA和分次TA给药均可有效抑制纤溶反应,显著减少术后6h出血量,并有明显的抑制炎性因子作用。

Objective To evaluate the effects of tranexamic acid（TA） on hemostasis and inflammatory mediators in cardiopulmonary in infants. Methods Infants weighted less than 10 kg undergoing cardiopulmonary bypass were investigated. The infants were randomly divided into three groups：TA1 group, TA2 group and control group. In the TA1 group, patients received tranexamic acid 30 mg·kg-1 after induction of anesthesia followed by continuous infusion at the rate of 16 mg·kg-1·h-1 and 2 mg·kg-1 in the pump prime. In the TA2 group, patients received TA 30 mg·kg-1 after induction of anesthesia, 30 mg·kg-1 in pump prime and 30 mg·kg-1 after weaning of bypass. In the control group, patients received the same volume saline. Blood loss and allogenic transfusion requirements during the period from the end of operation until 24 h after admission to the CICU were recorded. D-dimer was tested at four time points： before operation, during CPB, 6 and 24 h postoperatively.Interleukin-8, CRP and WBC counting were tested at five time points： before operation, at the end of operation（0 h）,6 ,12 and 24 h postoperatively. Results A total of 120 infants were recruited with 40 infants in each group. Baseline demographic data were similar among the groups. The blood loss was significantly lower in TA1 and TA2 groups than in control group within 6 h after operation（P0.05）, but there was no significant difference in blood loss during 24 h after operation. No difference was found in allogenic transfusion units among groups. D-dimer values increased from the beginning of CPB and remained higher till 24 h postoperatively among the three groups. The values in TA1 and TA2 groups were significantly lower than in control group at three time points： during CPB, 6 and 24 h postoperatively（P0.05）. Serum interleukin-8 level was elevated at the end of operation and remained higher until 12 h and began to drop 24 h postoperatively, however the level in control group remained greatly higher than that in TA1 and TA2 groups（P0.01）.The serum concentration of CRP was elevated obviously in 12 h after operation, and remained significantly higher in control group in 24 h postoperatively. No difference was found in WBC counting among three groups. Perioperative data and surgical complications did not show any difference among three groups. No mortality was observed in the study. Conclusions TA effectively reduce bleeding in early 6 h postoperatively and inhibit fibrinolysis and inflammation. Continuous infusion of TA does not show significant advantage to fractional dose.