Dani Carlo, Bertini Giovanna, Pezzati Marco, Poggi Chiara, Guerrini Pietro, Martano Claudio, Rubaltelli Firmino F
Department of Surgical and Medical Critical Care, Section of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
Pediatrics. 2005 Jun;115(6):1529-35. doi: 10.1542/peds.2004-1178.
Ibuprofen enhances cerebral blood flow autoregulation and was shown to protect neurologic functions after oxidative stresses in an animal model. For these reasons, we hypothesized that the prophylactic use of ibuprofen would reduce the occurrence of intraventricular hemorrhage (IVH) and its worsening toward grades 2 to 4 among preterm infants. To confirm this hypothesis, we planned the present prospective study.
This was a double-blind, randomized, controlled trial in which preterm infants with gestational ages of <28 weeks received ibuprofen or placebo within the first 6 hours of life. The infants were assigned randomly, at 7 neonatal care units, to receive ibuprofen (10 mg/kg, followed by 5 mg/kg after 24 and 48 hours) or placebo. Serial echoencephalography was performed 24 and 48 hours after the initial cerebral ultrasound study, on postnatal days 7, 15, and 30, and at 40 weeks' postconceptional age. Grade 1 IVH or no IVH was considered a successful outcome, whereas grade 2 to 4 IVH represented failure. The rates of ductal closure, side effects, and complications were recorded.
We studied 155 infants. Grade 2 to 4 IVH developed for 16% of the ibuprofen-treated infants and 13% of the infants in the placebo group. The occurrence of patent ductus arteriosus was less frequent only on day 3 of life in the ibuprofen group. There were no significant differences with respect to other complications or adverse effects.
Our study demonstrated that prophylactic ibuprofen is ineffective in preventing grade 2 to 4 IVH and that its use for this indication cannot be recommended.
布洛芬可增强脑血流自动调节功能，并且在动物模型中已显示其在氧化应激后能保护神经功能。基于这些原因，我们推测预防性使用布洛芬可减少早产儿脑室内出血（IVH）的发生及其向2至4级的恶化。为证实这一推测，我们开展了本前瞻性研究。
这是一项双盲、随机、对照试验，胎龄<28周的早产儿在出生后6小时内接受布洛芬或安慰剂治疗。在7个新生儿护理单位，婴儿被随机分配接受布洛芬（10mg/kg，24和48小时后各追加5mg/kg）或安慰剂。在初次脑超声检查后24和48小时、出生后第7天、第15天、第30天以及孕40周时进行系列脑回波描记术检查。1级IVH或无IVH被视为成功结局，而2至4级IVH代表失败。记录动脉导管闭合率、副作用和并发症情况。
我们研究了155名婴儿。布洛芬治疗组中16%的婴儿发生了2至4级IVH，安慰剂组中这一比例为13%。仅在出生后第3天，布洛芬组动脉导管未闭的发生率较低。在其他并发症或不良反应方面无显著差异。
我们的研究表明，预防性使用布洛芬在预防2至4级IVH方面无效，不推荐将其用于这一适应证。
