■先天性膈疝(CDH)通常与肺发育不全和肺动脉高压(PH)有关。与CDH相关的PH(CDH-PH)通常对常规的肺血管扩张剂治疗有抵抗力,包括吸入的一氧化氮(iNO)可能是由于右心室和左心室功能障碍。米力农是一种具有肺血管扩张剂特性的静脉内抗氧剂和抗氧剂,已被证明可以改善PH中的氧合。我们开展了这项初步研究,以确定米力农输注是否会改善患有CDH的月经后年龄≥36周(PMA)的新生儿的氧合。
■关于CDH患者的肺血管扩张剂管理和结果的数据收集自2011年至2012年与新生儿研究网络(NRN)相关的18所大学NICU。拟议的飞行员将是一个蒙面,安慰剂对照,多中心,对66例氧合指数(OI)≥10或氧饱和度指数(OSI)≥5的CDH婴儿进行随机试验。主要结果是氧合反应,根据研究药物开始后24小时OI的变化确定。作为次要结果,我们将在输注后48小时和72小时确定氧合,超声心动图右心室压和全身性低血压的发生率,心律失常,颅内出血,没有体外膜氧合的生存,和慢性肺病(出生后28天需要氧气)。最后,我们将使用电话问卷评估4,8和12月龄时的肺部和营养状况.
■2011年和2012年,三百三十七名患有CDH的婴儿进入NRNNICU,其中275名≥36周PMA,并暴露于以下肺血管扩张剂:iNO(39%),西地那非(17%),米力农(17%),吸入依前列醇(6%),静脉注射依前列醇(3%),和静脉注射PGE1(1%)。36%的患者需要ECMO。出院生存率为71%。
■CDH是一种死亡率高的孤儿病,很少有随机试验评估产后管理。静脉注射米力农是新生儿/儿科重症监护病房中常用的药物,目前在NRN内17%的CDH患者中使用。这项初步研究将提供数据,并使进一步的研究能够评估CDH中的肺血管扩张剂治疗。
■ClinicalTrials.gov;NCT02951130;2016年10月14日注册。
UNASSIGNED: Congenital diaphragmatic hernia (CDH) is commonly associated with pulmonary hypoplasia and pulmonary hypertension (PH). PH associated with CDH (CDH-PH) is frequently resistant to conventional pulmonary vasodilator therapy including inhaled nitric oxide (iNO) possibly due to right and left ventricular dysfunction. Milrinone is an intravenous inotrope and lusitrope with pulmonary vasodilator properties and has been shown anecdotally to improve oxygenation in PH. We developed this pilot study to determine if milrinone infusion would improve oxygenation in neonates ≥36 weeks postmenstrual age (PMA) with CDH.
UNASSIGNED: Data on pulmonary vasodilator management and outcome of CDH patients was collected from 18 university NICUs affiliated with the Neonatal Research Network (NRN) from 2011 to 2012. The proposed pilot will be a masked, placebo-controlled, multicenter, randomized trial of 66 infants with CDH with an oxygenation index (OI) ≥10 or oxygen saturation index (OSI) ≥5. The primary outcome is the oxygenation response, as determined by change in OI at 24 h after initiation of study drug. As secondary outcomes, we will determine oxygenation at 48 h and 72 h post-infusion, right ventricular pressures on echocardiogram and the incidence of systemic hypotension, arrhythmias, intracranial hemorrhage, survival without extracorporeal membrane oxygenation, and chronic lung disease (oxygen need at 28 days postnatal age). Finally, we will evaluate the pulmonary and nutritional status at 4, 8 and 12 months of age using a phone questionnaire.
UNASSIGNED: Three hundred thirty-seven infants with CDH were admitted to NRN NICUs in 2011 and 2012 of which 275 were ≥36 weeks PMA and were exposed to the following pulmonary vasodilators: iNO (39%), sildenafil (17%), milrinone (17%), inhaled epoprostenol (6%), intravenous epoprostenol (3%), and intravenous PGE1 (1%). ECMO was required in 36% of patients. Survival to discharge was 71%.
UNASSIGNED: CDH is an orphan disease with high mortality with few randomized trials evaluating postnatal management. Intravenous milrinone is a commonly used medication in neonatal/pediatric intensive care units and is currently used in 17% of patients with CDH within the NRN. This pilot study will provide data and enable further studies evaluating pulmonary vasodilator therapy in CDH.
UNASSIGNED: ClinicalTrials.gov; NCT02951130; registered 14 October 2016.