Van Overmeire Bart, Allegaert Karel, Casaer Alexandra, Debauche Christian, Decaluwé Wim, Jespers Ann, Weyler Joost, Harrewijn Inge, Langhendries Jean-Paul
Antwerp University Hospital, Edegem, Belgium.
Lancet. 2004;364(9449):1945-9. doi: 10.1016/S0140-6736(04)17477-1.
Ibuprofen is used for treatment and prevention of patent ductus arteriosus in low-birthweight infants. Its effects on regional circulations differ from those of indometacin. Because prophylactic indometacin reduces the frequency of severe intraventricular haemorrhage and patent ductus arteriosus, we aimed to study the efficacy of early ibuprofen in reducing these outcomes in a double-blind, multicentre trial.
Within 6 h after birth, 415 low-birthweight infants (gestational age <31 weeks) were randomly allocated ibuprofen-lysine (10 mg/kg then two doses of 5 mg/kg after 24 h and 48 h) or placebo intravenously. The primary outcome was occurrence of severe intraventricular haemorrhage; secondary outcomes were occurrence of patent ductus arteriosus and possible adverse effects of ibuprofen. Analysis was by intention to treat.
17 (8%) of 205 infants assigned ibuprofen and 18 (9%) of 210 assigned placebo developed severe intraventricular haemorrhage (relative risk 0.97 [95% CI 0.51-1.82]). In 172 (84%) infants of the ibuprofen group, the ductus was closed on day 3 compared with 126 (60%) of the placebo group (relative risk 1.40 [1.23-1.59]). No important differences in other outcomes or side-effects were noted; however, urine production was significantly lower on day 1 and concentration of creatinine in serum was significantly higher on day 3 after ibuprofen.
Ibuprofen prophylaxis in preterm infants does not reduce the frequency of intraventricular haemorrhage, but does decrease occurrence of patent ductus arteriosus.
布洛芬用于治疗和预防低体重儿动脉导管未闭。其对局部循环的影响与吲哚美辛不同。由于预防性使用吲哚美辛可降低严重脑室内出血和动脉导管未闭的发生率，我们旨在通过一项双盲、多中心试验研究早期使用布洛芬降低这些结局的疗效。
出生后6小时内，415名低体重儿（胎龄<31周）被随机静脉注射赖氨酸布洛芬（10mg/kg，然后在24小时和48小时后各注射5mg/kg两剂）或安慰剂。主要结局是严重脑室内出血的发生；次要结局是动脉导管未闭的发生以及布洛芬可能的不良反应。分析采用意向性治疗。
205名接受布洛芬治疗的婴儿中有17名（8%）发生严重脑室内出血，210名接受安慰剂治疗的婴儿中有18名（9%）发生严重脑室内出血（相对危险度0.97[95%可信区间0.51-1.82]）。布洛芬组172名（84%）婴儿在第3天动脉导管闭合，而安慰剂组为126名（60%）（相对危险度1.40[1.23-1.59]）。在其他结局或副作用方面未发现重要差异；然而，布洛芬治疗后第1天尿量显著降低，第3天血清肌酐浓度显著升高。
对早产儿预防性使用布洛芬不会降低脑室内出血的发生率，但会减少动脉导管未闭的发生。
