Gournay V, Roze J C, Kuster A, Daoud P, Cambonie G, Hascoet J M, Chamboux C, Blanc T, Fichtner C, Savagner C, Gouyon J B, Flurin V, Thiriez G
Service de Réanimation Pédiatrique et Néonatale, Hôpital de la Mère et de l'Enfant, Centre Hospitalier Universitaire (CHU) de Nantes, Quai Moncousu, 44000 Nantes, France.
Lancet. 2004;364(9449):1939-44. doi: 10.1016/S0140-6736(04)17476-X.
Patent ductus arteriosus is a common complication of prematurity that frequently requires surgical or medical treatment. The benefit of prophylactic treatment by indometacin, a cyclo-oxygenase inhibitor, remains uncertain compared with curative treatment. This benefit could be improved with ibuprofen, another cyclo-oxygenase inhibitor with fewer adverse effects than indometacin on renal, mesenteric, and cerebral perfusion. We aimed to compare prophylactic and curative ibuprofen in the treatment of this abnormality in very premature infants.
We did a randomised controlled trial in infants younger than 28 weeks of gestation, who were randomly assigned to receive either three doses of ibuprofen or placebo within 6 h of birth. After day 3, symptomatic patent ductus arteriosus was treated first by open curative ibuprofen, then back-up indometacin, surgery, or both. The primary endpoint was need for surgical ligation. Analysis was per protocol.
The study was stopped prematurely after 135 enrollments because of three cases of severe pulmonary hypertension in the prophylactic group. 65 infants received prophylactic ibuprofen, and 66 received placebo. Prophylaxis reduced the need for surgical ligation from six (9%) to zero (p=0.03), and decreased the rate of severe intraventricular haemorrhage from 15 (23%) to seven (11%) (p=0.10). However, survival was not improved (47 [71%] placebo vs 47 [72%] treatment, p=1.00), because of high frequency of adverse respiratory, renal, and digestive events.
In premature infants, prophylactic ibuprofen reduces the need for surgical ligation of patent ductus arteriosus, but does not reduce mortality or morbidity. Therefore, it should not be preferred to early curative ibuprofen.
动脉导管未闭是早产常见的并发症，常需手术或药物治疗。与根治性治疗相比，环氧化酶抑制剂吲哚美辛预防性治疗的益处仍不确定。布洛芬是另一种环氧化酶抑制剂，对肾、肠系膜和脑灌注的不良反应比吲哚美辛少，可能会提高这种益处。我们旨在比较预防性和根治性使用布洛芬治疗极早产儿的这种异常情况。
我们对妊娠小于28周的婴儿进行了一项随机对照试验，这些婴儿在出生后6小时内被随机分配接受三剂布洛芬或安慰剂。3天后，有症状的动脉导管未闭首先采用根治性布洛芬开放治疗，然后备用吲哚美辛、手术或两者联合治疗。主要终点是是否需要手术结扎。分析按方案进行。
在纳入135例患者后，该研究因预防组出现3例严重肺动脉高压而提前终止。65例婴儿接受预防性布洛芬治疗，66例接受安慰剂治疗。预防措施将手术结扎的需求从6例（9%）降至0例（p=0.03），并将重度脑室内出血的发生率从15例（23%）降至7例（11%）（p=0.10）。然而，由于不良呼吸、肾脏和消化事件的发生率较高，生存率没有提高（安慰剂组47例[71%]，治疗组47例[72%]，p=1.00）。
在早产儿中，预防性使用布洛芬可减少动脉导管未闭的手术结扎需求，但不能降低死亡率或发病率。因此，它不应优先于早期根治性使用布洛芬。
