Mercanti Isabelle, Boubred Farid, Simeoni Umberto
Division of Neonatalogy, Children and Parents Pole, Assistance Publique - Hôpitaux de Marseille & Université de la Méditerranée, Marseille, France.
J Matern Fetal Neonatal Med. 2009;22 Suppl 3:14-20. doi: 10.1080/14767050903198132.
Patency of the ductus arteriosus (PDA), a common complication of preterm birth, has been associated to increased risk for intraventricular cerebral hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia and death. Consequently, prophylactic or curative treatment has been advocated before the critical left-to-right shunting occurs. A host of studies has shown that both pharmacological agents and surgical closure are effective in closing the ductus arteriosus in premature infants. Indomethacin has long been the drug of choice. However, renal and cerebral haemodynamic side effects have been frequently reported. Strategies to minimise adverse effects of indomethacin, such as the association with frusemide, dopamine or the use of low-dose prolonged treatment with indomethacin have failed or shown partial benefit. Other NSAIDs have been investigated. But either the profile of adverse effects was unfavourable, as in the case of mefenamic acid, or their efficacy was less than that of indomethacin for PDA closure. More recently, ibuprofen has been proposed for the treatment of PDA as it was shown to induce less adverse effects on cerebral blood flow, intestinal and renal hemodynamics, while retaining similar efficacy to indomethacin. However, since renal perfusion, GFR and diuresis in early neonatal life strongly depend on the vasodilator effects of PGs on the afferent glomerular arterioles, ibuprofen, as other COX-inhibitors may not be exempt of some renal undesirable effects. While numerous studies have shown that PDA is a risk factor associated with immaturity and with increased incidence of complications of preterm birth, including broncho-pulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis and death, there is little evidence that such association is causative. Moreover, still little evidence exists from even recent randomized controlled trials that the pharmacological closure of PDA benefits to premature infants in terms of clinically significant short-term or medium-term outcomes, beyond a positive effect on DA patency. The use of COX-inhibitors for the prophylaxis or closure of PDA during the first hours or days of life should thus be cautious and based on an individual evaluation of benefit and risk. There is need of a randomized, placebo-controlled trials designed to assess the benefits in terms of mortality and morbidity outcomes of an early, or even very early pharmacological closure of PDA in extremely low gestational age infants.
动脉导管未闭（PDA）是早产的常见并发症，与脑室内出血、坏死性小肠结肠炎、支气管肺发育不良和死亡风险增加相关。因此，在关键的左向右分流发生之前，一直提倡进行预防性或治疗性治疗。大量研究表明，药物治疗和手术闭合在闭合早产儿动脉导管方面均有效。吲哚美辛长期以来一直是首选药物。然而，肾和脑血流动力学副作用屡有报道。尽量减少吲哚美辛不良反应的策略，如与呋塞米、多巴胺联合使用或使用低剂量延长疗程的吲哚美辛治疗，均告失败或仅显示部分益处。已对其他非甾体抗炎药进行了研究。但要么不良反应情况不佳，如甲芬那酸，要么其对闭合PDA的疗效低于吲哚美辛。最近，布洛芬已被提议用于治疗PDA，因为它对脑血流、肠道和肾血流动力学的不良影响较小，同时保留了与吲哚美辛相似的疗效。然而，由于新生儿早期的肾灌注、肾小球滤过率和利尿作用强烈依赖于前列腺素对肾小球入球小动脉的血管舒张作用，布洛芬与其他环氧化酶抑制剂一样，可能无法避免一些不良肾脏影响。虽然众多研究表明PDA是与早产不成熟及并发症发生率增加相关的危险因素，包括支气管肺发育不良、早产儿视网膜病变、坏死性小肠结肠炎和死亡，但几乎没有证据表明这种关联具有因果关系。此外，即使是最近的随机对照试验也几乎没有证据表明，PDA的药物闭合在临床上显著的短期或中期结局方面对早产儿有益，超出了对动脉导管通畅的积极影响。因此，在生命的最初数小时或数天内使用环氧化酶抑制剂预防或闭合PDA应谨慎，并基于对益处和风险的个体评估。需要进行一项随机、安慰剂对照试验，以评估在极低孕周婴儿中早期甚至极早期药物闭合PDA在死亡率和发病率结局方面的益处。
