König Kai, Barfield Charles P, Guy Katelyn J, Drew Sandra M, Andersen Chad C
Mercy Hospital for Women, Department of Paediatrics , Melbourne, Victoria , Australia and.
J Matern Fetal Neonatal Med. 2014 Mar;27(5):439-44. doi: 10.3109/14767058.2013.818650. Epub 2013 Aug 8.
Sildenafil has been shown to preserve alveolar growth and lung angiogenesis in a rat model of bronchopulmonary dysplasia. We conducted a proof-of-concept randomised controlled pilot study to assess the feasibility of oral sildenafil treatment in extremely preterm infants with evolving bronchopulmonary dysplasia.
Preterm infants <28 weeks gestational age were eligible if they were mechanically ventilated on day 7 of life. Infants were randomised to a 4-weeks course of either oral sildenafil (3 mg/kg/day) or placebo solution. Pre-discharge cardiorespiratory outcomes and medication side effects were collected.
Twenty infants were randomised, 10 received sildenafil (mean gestational age 24 + 5 weeks (SD 4.9 days), mean weight 692 g (SD 98)) and 10 received placebo (mean gestational age 24 + 5 weeks (SD 6.5 days), mean weight 668 g (SD 147)). One infant in the sildenafil group did not receive treatment because of an early pneumoperitoneum. Two infants did not complete the study (transferred out). Of the remaining seven treated infants, three died (two from respiratory-related causes). One infant in the control group died from a non-respiratory cause. Sildenafil did not reduce length of invasive (median 688 versus 227 h) or non-invasive ventilation (median 1609 versus 1416 h). More infants in the sildenafil group required postnatal steroid treatment. One infant developed hypotension following sildenafil administration and was excluded after three doses.
In this pilot study, oral sildenafil treatment did not improve any short-term respiratory outcomes in extremely preterm infants.
在支气管肺发育不良的大鼠模型中，已证实西地那非可促进肺泡生长和肺血管生成。我们开展了一项概念验证性随机对照试验性研究，以评估口服西地那非治疗极早产儿进展性支气管肺发育不良的可行性。
孕龄<28周的早产儿若在出生第7天接受机械通气则符合入选标准。婴儿被随机分为两组，分别接受为期4周的口服西地那非（3毫克/千克/天）或安慰剂溶液治疗。收集出院前的心肺结局和药物副作用。
20名婴儿被随机分组，10名接受西地那非治疗（平均孕龄24 + 5周（标准差4.9天），平均体重692克（标准差98）），10名接受安慰剂治疗（平均孕龄24 + 5周（标准差6.5天），平均体重668克（标准差147））。西地那非组有1名婴儿因早期气腹未接受治疗。2名婴儿未完成研究（转出）。其余7名接受治疗的婴儿中，3名死亡（2名死于呼吸相关原因）。对照组有1名婴儿死于非呼吸原因。西地那非并未缩短有创通气时长（中位数688小时对227小时）或无创通气时长（中位数1609小时对1416小时）。西地那非组更多婴儿需要出生后使用类固醇治疗。1名婴儿在服用西地那非后出现低血压，在服用三剂后被排除。
在这项试验性研究中，口服西地那非治疗并未改善极早产儿的任何短期呼吸结局。
