口服布洛芬治疗早产儿动脉导管未闭疗效和安全性的meta分析

Efficacy and safety of oral ibuprofen for closure of patent ductus arteriosus in preterm infants： a metaanalysis

目的评价口服布洛芬治疗早产儿动脉导管未闭（patent ductus arteriosus，PDA）的疗效和安全性。方法检索Cochrane图书馆临床对照试验数据库、PubMed、EMBASE、Ovid、Springer、中国期刊全文数据库、万方数据库、维普数据库及中国生物医学文献光盘数据库从建库至2011年12月31日的所有文献。同时手工检索会议记录和专题论文集，资料来源于复旦大学附属儿科医院。同时满足以下条件的文献被纳人：（1）研究对象为出生胎龄〈37周和／或出生体重〈2500g的早产儿；（2）随机或半随机对照研究；（3）研究组干预类型为经肠道给予布洛芬，对照组为经肠道给予安慰剂或静脉应用吲哚美辛或布洛芬；（4）主要研究结果为PDA关闭失败率；（5）超声证实存在血流动力学改变的PDA。采用Review Manager4．22软件进行meta分析。结果共纳入11篇文献，均为随机临床对照研究，其中3篇文献质量较高。Meta分析表明，与安慰剂组相比，口服布洛芬早产儿PDA关闭失败率显著降低（RR=0．22，95％CI：0．14～0．35），且需要手术治疗PDA的患儿比例明显减少（RR=0．16，95％CI：0．03～0．86）。口服布洛芬关闭早产儿PDA的疗效与静脉应用吲哚美辛相似（RR=0．93，95％CI：0．57～1．53），而优于静脉应用布洛芬（RR=0．42，95％CI：0．26～0．67）。与静脉应用吲哚美辛或布洛芬相比，口服布洛芬并不能减少需要手术治疗的早产儿PDA比例（RR=0．58，95％CI：0．24～1．41）。口服布洛芬与安慰剂比较，消化道出血的发生率显著增加（RR一1．99，95％CI：1．13～3．50）。口服布洛芬组血清肌酐水平显著低于静脉应用吲哚美辛或静脉应用布洛芬组（加权平均差=-19．10，95％CI：-25．12～12．31）。与静脉应用吲哚美辛组比较，口服布洛芬组发生新生儿坏死性小肠结肠炎的比例较小，但2组的差异无统计学意义（RR=0．57，95％CI：0．30～1．09）。所有文献均未报道远期预后。结论口服布洛芬具有较好的早产儿PDA关闭率，疗效与静脉应用吲哚美辛一致，且优于静脉应用布洛芬；早产儿口服布洛芬安全性较好。

Objective To evaluate the efficacy and safety of oral ibuprofen for closure of patent ductus arteriosus （PDA） in preterm infants. Methods The related literatures till December 31st, 2011 in Cochrane Library, PubMed, EMBASE, Ovid, Springer, China Academic Journal Full-text Database, Wanfang Database, VlP Database and China Biological Medical Literature Database were searched. The inclusion criteria were： （1） the subject of the research was preterm infants with birth weight less than 2500 g and/or gestational age less than 37 weeks; （2） randomized or semi- randomized controlled trial; （3） the intervention group received oral ihuprofen, while the control group received oral placebos / intravenous indomethacin or ibuprofen; （4） the main outcome was the failure rate of PDA closure; （5） hemodynamic changes with PDA were detected by ultrasonography. Meta-analysis was performed by Review Manager 4. 22 software. Results Eleven randomized controlled trials were included, among which, three were high quality reports. Meta-analysis showed lower failure rate of PDA closure in subjects received oral ibuprofen than in those received placebos orally （RR = 0.22,95 % CllO. 14-0.35）, while the number of infants required operative closure of PDA decreased significantly （RR = O. 16,95 % CI ： 0. 03-0. 86）. Further analysis showed the effect of oral ibuprofen was similar to intravenous indomethacin （RR=0.93,95%CI：0.57-1.53）, but better than intravenous ibuprofen （RR=0.42,95%CI：0.26-0.67）. However, oral ibuprofen did not reduced the ratio of patients required operation compared with intravenous indomethacin or ibuprofen （RR=0.58, 95%CI ：0. 24-1. 41）. The incidence of gastrointestinal hemorrhage was higher in oral ibuprofen group than that in placebos（RR= 1.99,95%CI： 1.13-3.50）. The serum level of creatine was lower in oral ibuprofen group than in intravenous indomethacin or ibuprofen group （weighted average=--19.10, 95% CI..- 25.12-12.31）. Compared with intravenous indomethcin group, less necrotizing enterocolitis cases were identified in oral ibuprofen group, but no statistical significance was found （RR= 0. 57,95% CI： 0. 30-1.09）. No long-term outcome was reported in any selected literature. Conclusions Oral ibuprofen for PDA closure in preterm infants appears to be as effective as intravenous or indomethacin, and more effective than intraveous ibuproten. Oral ibuproten represents better safety.