Heyman Eli, Morag Iris, Batash David, Keidar Rimona, Baram Shaul, Berkovitch Matitiahu
Neonatal Intensive Care Unit, Assaf Harofeh Medical Center, Zerifin, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Pediatrics. 2003 Nov;112(5):e354. doi: 10.1542/peds.112.5.e354.
Patent ductus arteriosus (PDA), a common finding among premature infants, is conventionally treated by intravenous indomethacin. Intravenous ibuprofen was recently shown to be as effective and to have fewer adverse reactions in preterm infants. If equally effective, then oral ibuprofen for PDA closure would have several important advantages over the intravenous route. This study was designed to determine whether oral ibuprofen treatment is efficacious and safe in closure of a PDA in premature infants with respiratory distress syndrome.
Twenty-two preterm newborns (gestational age: 27.5 +/- 1.75 [range: 23.9-31 weeks]; weight: 979 +/- 266 [range: 380-1500 g]) with PDA and respiratory distress syndrome were studied prospectively. They received oral ibuprofen suspension 10 mg/kg/body weight for the first dose, followed at 24-hour intervals by 2 additional doses of 5 mg/kg each, if needed, starting on the second day of life. Echocardiography was performed before treatment and 24 hours after each dose. Every child underwent cranial ultrasonography before and after each ibuprofen dose. The rate of ductal closure, the need for additional treatment, side effects, complications, and the infants' clinical courses were recorded.
Ductal closure was achieved in all newborns except for 1 (95.5%), in whom clinically nonsignificant ductal shunting persisted. No infant required surgical ligation of the ductus. There was no reopening of the ductus after closure had been achieved. Fourteen newborns were treated with 1 dose of ibuprofen, 6 were treated with 2 doses, and the remaining 2 were treated with 3 doses. The survival rate at 1 month was 86.4% (19 of 22). Three (13.6%) infants died from the following causes: 1 who was born at 24 weeks' gestation with a birth weight of 380 g died as a result of extreme prematurity complications, necrotizing enterocolitis, and low birth weight; 1 died as a result of Candida sepsis; and the third died as a result of Klebsiella sepsis. Intraventricular hemorrhage was observed in 7 infants. The classification was changed from grade 2 to grade 3 in 1 and from grade 0 to grade 1 or higher in 3 others. The rate of survival to discharge was 86.4% (19 of 22). No bronchopulmonary dysplasia was observed in the study group, and there was no case of tendency to bleed. There were no significant differences in the levels of serum creatinine before and after treatment with oral ibuprofen.
Oral ibuprofen suspension may be an effective and safe alternative for PDA closure in premature infants with PDA. However, larger comparative studies are warranted.
动脉导管未闭（PDA）是早产儿中的常见病症，传统上采用静脉注射吲哚美辛进行治疗。最近研究表明，静脉注射布洛芬对早产儿同样有效且不良反应较少。若效果相同，那么口服布洛芬治疗PDA闭合相较于静脉途径具有几个重要优势。本研究旨在确定口服布洛芬治疗呼吸窘迫综合征早产儿的PDA闭合是否有效且安全。
对22例患有PDA和呼吸窘迫综合征的早产新生儿（胎龄：27.5±1.75[范围：23.9 - 31周]；体重：979±266[范围：380 - 1500克]）进行前瞻性研究。他们在出生第二天开始，首剂口服布洛芬混悬液10毫克/千克体重，如有需要，每隔24小时再额外给予2剂，每剂5毫克/千克。治疗前及每次给药后24小时进行超声心动图检查。每次布洛芬给药前后，每个患儿均接受头颅超声检查。记录动脉导管闭合率、额外治疗需求、副作用、并发症及婴儿的临床病程。
除1例（95.5%）外，所有新生儿均实现动脉导管闭合，该例患儿存在临床上无显著意义的动脉导管分流。无婴儿需要进行动脉导管手术结扎。动脉导管闭合后未再重新开放。14例新生儿接受1剂布洛芬治疗，6例接受2剂治疗，其余2例接受3剂治疗。1个月时的生存率为86.4%（22例中的19例）。3例（13.6%）婴儿因以下原因死亡：1例孕24周出生，出生体重380克，死于极早早产并发症、坏死性小肠结肠炎及低出生体重；1例死于念珠菌败血症；第3例死于克雷伯菌败血症。7例婴儿观察到脑室内出血。其中1例从2级变为3级，另外3例从0级变为1级或更高级别。出院生存率为86.4%（22例中的19例）。研究组未观察到支气管肺发育不良，也无出血倾向病例。口服布洛芬治疗前后血清肌酐水平无显著差异。
口服布洛芬混悬液可能是治疗患有PDA的早产儿PDA闭合的一种有效且安全的替代方法。然而，需要进行更大规模的对比研究。
