口服布洛芬治疗早产儿动脉导管未闭的前瞻性随机对照研究

Oral ibuprofen treatment for patent ductus arteriosus in premature infants： a prospective randomized controlled trial

目的研究口服布洛芬在早产儿动脉导管未闭（patent ductus arteriosus，PDA）治疗中的安全性、治疗效果和副作用，以评估其在早产儿PDA治疗中的应用价值。方法采用前瞻性随机对照研究方法，根据PDA诊断的时间顺序，按随机数字顺序表，将74例PDA早产儿随机分为布洛芬治疗组（36例）与对照组（38例），布洛芬治疗方法为口服布洛芬混悬液每剂10mg／kg，间隔24h1次，共3次；记录并比较2组PDA的关闭率、相关副作用及患儿住院期间的情况。结果布洛芬治疗组PDA关闭率为52．8％（19／36），高于对照组（18．4％，7／38），差异有统计学意义（x2=9．575，P=0．002）。在口服布洛芬治疗期间，患儿未出现少尿、肾功能损害、出血倾向、胃肠道穿孔、Ⅲ或Ⅳ级脑室内出血或出血加重等严重副作用，布洛芬治疗组和对照组出现腹胀或胃潴留的发生率分别为33．3％（12／36）和26．3％（10／38），差异无统计学意义（x2=0．436，P=0．509）。布洛芬治疗组患儿平均住院（22．8±14．8）d，用氧（8．3±9．3）d，5.6％（2／36）需要机械通气，与对照组[分别为（24．1±17．1）d、（8．8±8．3）d和2．6％（1／38）]比较差异均无统计学意义（P均〉0．05）。结论口服布洛芬对早产儿PDA有较好的治疗效果，且无明显合并症或副作用发生，应用方便，安全性较高。

Objective To assess the safety, efficacy, temporary side effects and feasibility of oral ibuprofen suspension in the treatment of patent ductus arteriosus （PDA） with hemodynamic significance in premature infants. Method A randomized controlled trial including seventy four premature infants with PDA was performed from February 2007 to May 2008. Infants were randomly assigned to two groups： testing group （36 patients） received three doses of oral ibuprofen suspension （10 mg/kg at 24-hour intervals） and control group （38 patients） did not receive such treatment. The cure rate of PDA, relative side effects of ibuprofen and complications during treatment were recorded. Results The closure rate of ductus arteriosus in the testing group was 52.8% （19/36）, which was higher than that of control group （18.4%, 7/38） （x2 =9. 575, P=0. 002）. The severe side effects did not occur in testing group, such as oliguria, renal impairment, prone of bleeding, gastrointestinal perforation and novel appearing or deteriorative of intraventricular hemorrhage （IVH）. Compared with the infants in control group （26. 3%, 10/38）, the morbidity of abdominal distension or gastric retention in testing group （33. 3%, 12/36） was higher, while there was no statistically significant difference （x2=0. 436, P=0. 509）. The hospital stay [（22. 8±14.8） d vs （24. 1±17. 1） d], mechanical Ventilation rate [5.6% （2/36） vs 2.6% （1/38）] and oxygen supplement time [（8.3 ± 9.3） d vs （8. 8±8.3） d] between the testing and control groups remained no significant difference （P〉0. 05）. Conclusions Oral ibuprofen suspension could be effective in closing PDA of preterm infants; no significant complications and side-effects occurred during oral ibuprofen treatment. It is suggested that oral ibuprofen suspension treatment was safe, effective and well tolerated for preterm infants with PDA.