Pediatric Cardiology and Pulmonology Department, M3C Regional Referral CHD Center, University Hospital, Montpellier, France.
PhyMedExp, CNRS, INSERM, University of Montpellier, Montpellier, France.
J Cardiovasc Pharmacol. 2020 Jul;76(1):23-31. doi: 10.1097/FJC.0000000000000820.
Add-on therapy with prostacyclin in pediatric refractory pulmonary hypertension (PH) poses a challenge, especially when considering continuous intravenous administration in younger children. A search for alternate routes of drug delivery has led to the clinical investigation of stable and long-acting prostacyclin analogues, such as subcutaneous treprostinil. We reported 2 pediatric cases of PH treated with subcutaneous treprostinil and reviewed the literature on treprostinil use in children.
The literature review used 3 electronic databases and a combination of terms (treprostinil, pediatric, PH, prostanoid, etc). We also searched for pediatric clinical trials on treprostinil registered on international clinical trial registries.
The reported cases highlighted the multifactorial nature of PH in pediatrics: a female child with a giant omphalocele, and intracardiac and extracardiac shunts; and a male premature child with a congenital diaphragmatic hernia and long-term PH. The literature review identified 19 studies reporting treprostinil use in 421 children with various types of PH (groups 1 and 3). Subcutaneous treprostinil was the most administered formulation, at a mean dose of 40 ng/kg/min. Overall, 12 clinical trials on treprostinil for children with PH were registered on the clinical trial registries. Most authors concluded that subcutaneous treprostinil was effective, well tolerated, and represented an alternative to intravenous epoprostenol.
Subcutaneous treprostinil may be a useful adjunct in the therapeutic algorithm for children with severe PH, refractory to oral drugs, and after a complete check-up for all PH etiologies.
在儿科难治性肺动脉高压（PH）中添加前列环素治疗是一个挑战，尤其是在考虑对较小的儿童进行连续静脉内给药时。寻找替代的药物输送途径导致了对稳定和长效前列环素类似物的临床研究，如皮下曲前列尼尔。我们报告了 2 例 PH 患儿使用皮下曲前列尼尔治疗的病例，并回顾了曲前列尼尔在儿童中的应用文献。
文献综述使用了 3 个电子数据库和组合术语（曲前列尼尔、儿科、PH、前列腺素等）。我们还搜索了在国际临床试验注册中心注册的曲前列尼尔儿科临床试验。
报告的病例突出了儿科 PH 的多因素性质：一名女性患儿患有巨大脐膨出，伴有心内和心外分流；一名男性早产儿患有先天性膈疝和长期 PH。文献综述确定了 19 项研究报告了 421 例不同类型 PH（第 1 组和第 3 组）患儿使用曲前列尼尔。皮下曲前列尼尔是最常用的制剂，平均剂量为 40ng/kg/min。总体而言，有 12 项关于儿童 PH 的曲前列尼尔临床试验在临床试验注册中心注册。大多数作者得出结论，皮下曲前列尼尔是有效的，耐受性良好，是静脉内依前列醇的替代方案。
皮下曲前列尼尔可能是治疗对口服药物难治性严重 PH 儿童的有用辅助手段，并且在对所有 PH 病因进行全面检查后使用。
