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Is it really pphn? Think before starting sildenafil!

INDIAN PEDIATRICS 2012年第12期49卷 987-988页

作者： Tomar, Munesh Bajpai, Pankaj Medanta The Medicity Dept Pediat Cardiol & Congenital Heart Dis Gurgaon Haryana India

The use of sildenafil has become a common practice in neonatal intensive care unit on clinical ground, because opinion by Pediatric Cardiologist is usually not available especially in peripheral centers. We consider it essential to share our experience that severe pulmonary arterial hypertension can be due to some unusual hemodynamics or extremely rare structural causes which do not require pulmonary vasodilator therapy.

关键词： Echocardiography pphn Pulmonary veins stenosis Vein of Galen malformation

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Effectiveness of oral sildenafil for neonates with persistent pulmonary hypertension of newborn (pphn): a prospective study in a tertiary care hospital

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JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE 2022年第25期35卷 6787-6793页

作者： Kamran, Amber Rafiq, Nida Khalid, Adeel Amin, Fatima Kumari, Veena Shaikh, Abdul Sattar Tebha, Sameer Saleem Patel, Najma Natl Inst Cardiovasc Dis Dept Pediat Cardiol Karachi Pakistan Jinnah Med & Dent Coll Dept Neurosurg & Neurol Karachi 74000 Pakistan

Introduction: The prevalence of persistent pulmonary hypertension of newborn (pphn) has been estimated 1.9/1000 live births. Although the efficacy of inhaled nitric oxide and extracorporeal membrane oxygenation in pphn is well established but it is difficult to administer and monitor in resource limited countries. Owing to this, other treatment options need to be evaluated. Method: This is a prospective observational study conducted in the Pediatric Cardiology Department, NICVD, Karachi, from February 2020 to October 2020 after the approval from the Institutional Ethical Review Committee. All the neonates referred to our Unit were screened by echocardiography (echo) and those who fulfilled the inclusion criteria were included. Echo were done before starting sildenafil and after 72 h to assess the pressure gradient across tricuspid valve and right to left or bidirectional shunt across patent ductus arteriosus, patent foramen ovale, or both. Sildenafil was started with a dose of 1 mg/kg/dose thrice a day and increased to 2mg/kg/dose after 48 h if partial pressure of oxygen (PO1] did not increase. In neonates who did not respond to increased dose of Sildenafil were added on oral Bosentan 1mg/kg/dose twice a day. Results: Total 82 newborns were enrolled. Fifty-two patients improved after 48 h so were continued on same treatment. Sildenafil dose was increased in 30 (37.9%) patients whose PO2 did not increase to at least 10% from baseline after 48 h of starting treatment. Three patients expired within 48-72 h. Out of 27 remaining patients, only four responded whereas 23 patients did not show any improvement. In these patients, Bosentan was supplemented along with sildenafil. Conclusion: The results of our study show effectiveness of oral Sildenafil in treating pphn. The overall improvement observed in the patients was overwhelming. Combination of Sildenafil with Bosentan is beneficial in patients who did not respond on Sildenafil alone.

关键词： pphn sildenafil pulmonary hypertension neonate bosentan

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Efficacy and Safety of IV Sildenafil in the Treatment of Newborn Infants with, or at Risk of, Persistent Pulmonary Hypertension of the Newborn (pphn): A Multicenter, Randomized, Placebo-Controlled Trial

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JOURNAL OF PEDIATRICS 2021年 237卷 154-+页

作者： Pierce, Christine M. Zhang, Min H. Jonsson, Baldvin Iorga, Dinu Cheruvu, Narayan Balagtas, Cecile C. Steinhorn, Robin H. Great Ormond St Hosp Sick Children Pediat & Neonatal Intens Care London England Pfizer Inc Global Biometr & Data Management La Jolla CA USA Karolinska Inst Dept Neonatol Stockholm Sweden Univ Hosp Stockholm Sweden Pfizer Inc Collegeville PA USA Pfizer Inc New York NY USA Rady Childrens Hosp San Diego CA USA Univ Calif San Diego San Diego CA 92103 USA

Objective To investigate the efficacy and safety of sildenafil added to inhaled nitric oxide (iNO) for newborn infants with persistent pulmonary hypertension of newborn (pphn) or hypoxic respiratory failure (HRF) at risk of pphn. Study design Part A of a multinational, randomized, double-blind, placebo-controlled trial. Infants <= 96 hours' old, >34 weeks of gestation, receiving iNO (10-20 ppm on >= 50% FiO(2)) for pphn or HRF at risk of pphn, and oxygen index >15 to <60, were randomized (1:1) to intravenous (IV) sildenafil (loading: 0.1 mg/kg, over 30 minutes;maintenance: 0.03 mg/kg/h) or placebo, for up to 14 days. Coprimary end points were treatment failure rate (day 14/ discharge) and time on iNO without treatment failure. Secondary end points included time on ventilation and oxygenation measures. Results Of 87 infants screened, 29 were randomized to IV sildenafil and 30 to placebo;13 discontinued treatment (sildenafil, n = 6;placebo: n = 7), including 3 deaths (sildenafil: n = 2;placebo: n = 1). Treatment failure rates did not differ with sildenafil (27.6%) vs placebo (20.0%;P =.4935). Mean time on iNO was not different with sildenafil (4.1 days) vs placebo (4.1 days;P =.9850). No differences were noted in secondary end points. Most common adverse events (AEs) with sildenafil (>= 10% infants) were hypotension (n = 8/29), hypokalemia (n = 7/29), anemia, drug withdrawal syndrome (n = 4/29, each), and bradycardia (n = 3/29). One serious AE (hypotension) was considered treatment-related. Conclusions IV sildenafil added to iNO was not superior to placebo in infants with pphn or HRF at risk of pphn. A review of AEs did not identify any pattern of events indicative of a safety concern with IV sildenafil. Infants will have developmental follow-up (Part B).

关键词： sildenafil citrate pphn placebo infant inhaled nitric oxide treatment failure

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胸阻抗法无创血流动力学监测评估pphn患儿心功能的临床研究

胸阻抗法无创血流动力学监测评估PPHN患儿心功能的临床研究

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作者：董伟济南大学

学位级别：硕士

目的:探讨阻抗法无创血流动力学监测对持续性肺动脉高压患儿心功能评估的价值。研究方法:2017年1月至2018年12月住院的新生儿60例,根据是否存在新生儿持续性肺动脉高压,分为pphn组(30例)、对照组(30例),采用阻抗法无创血流动力学及心脏... 详细信息

目的:探讨阻抗法无创血流动力学监测对持续性肺动脉高压患儿心功能评估的价值。研究方法:2017年1月至2018年12月住院的新生儿60例,根据是否存在新生儿持续性肺动脉高压,分为pphn组(30例)、对照组(30例),采用阻抗法无创血流动力学及心脏彩超进行检测,无创血流动力学监测仪监测SV(每搏输出量)、CO(心排血量)、STR(收缩时间比)、ICON(心肌收缩指数)、TFC(胸腔液体水平)、FTC(校正的射血时间),彩色超声多普勒获得右室内径、左室舒张末期内径、左房内径、右房宽径、右房长径、肺动脉主干内径、EF,进行差异性及相关性分析。结果:(1)心脏彩超监测数据:pphn组与对照组,右室内径、肺动脉主干、右房宽径、右房长径均显著高于对照组,P<0.05。pphn组左心室舒张末期内径小于对照组,P<0.05,差异有统计学意义。EF两组数值无明显差异。(2)胸阻抗法监测数据:pphn组与对照组,pphn组中SV、FTC、CO、ICON明显低于对照组,STR显著高于对照组,P<0.05,差异有统计学意义。其中两组TFC数据,P>0.05,差异无统计学意义。(3)pphn组胸阻抗法检测结果与心脏超声检测结果的相关性分析:SV、CO与肺动脉主干、右房宽径及右房长径负相关,SV、CO与左室舒张末期内径、左房内径正相关。FTC与左心室舒张末期内径以及左房内径呈负相关。STR与肺动脉主干内径以及右房宽径、右房长径正相关。ICON、TFC与各项指标无相关性。结论:pphn组患儿出现心功能障碍前常不出现射血分数的明显下降,心脏彩超检测可发现房室内径的变化,而胸阻抗法能有效的检测pphn患儿血流动力学改变,在心脏彩超尚不能检测到射血分数下降前,胸阻抗法可发现SV、CO、STR、ICON以及FTC的变化,能够更敏感的发现指标的异常。胸阻抗法血流动力学监测能评估pphn患儿心功能状态,胸阻抗法与心脏彩超检测指标有良好的相关性,两者可以有效的互补,为pphn患儿的心功能评估提供更多的血流动力学的参数。

关键词：胸阻抗法 pphn 无创血流动力学监测心功能

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高频振荡通气联合多巴胺治疗pphn的效果及对氧合指数、D-D水平的影响

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数理医药学杂志 2020年第6期33卷 857-859页

作者：蔡云开封市杞县妇幼保健院开封475200

目的:探讨高频振荡通气(HFOV)联合多巴胺治疗新生儿持续性肺动脉高压(pphn)的效果及对氧合指数(OI)、D-二聚体(D-D)水平的影响。方法:选取2018年2月~2019年2月某院收治的90例pphn患儿为对象,按照随机数字法分为对照组(n=45)和观察组(n=4... 详细信息

目的:探讨高频振荡通气(HFOV)联合多巴胺治疗新生儿持续性肺动脉高压(pphn)的效果及对氧合指数(OI)、D-二聚体(D-D)水平的影响。方法:选取2018年2月~2019年2月某院收治的90例pphn患儿为对象,按照随机数字法分为对照组(n=45)和观察组(n=45),对照组给予HFOV治疗,观察组给补高频振荡通气联合多多巴胺治疗,比较两组临床疗效,血氧饱和度(SpO2)、OI、血清C反应蛋白(CRP)、脑钠肽(BNP)、D-D水平的变化。结果:治疗后观察组总有效率为93.33%显著高于对照组的71.11%(P<0.05);治疗后观察组OI低于对照组,SpO2高于对照组(P<0.05);治疗后观察组血清CRP、BNP及D-D水平均显著低于对照组(P<0.05)。结论:HFOV联合多巴胺治疗pphn的效果显著,能够改善机体缺氧状态,降低炎性因子。

关键词： pphn 高频振荡通气多多巴胺氧合指数 D-D水平

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高频振动通气治疗新生儿pphn 26例体会

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中国冶金工业医学杂志 2017年第4期34卷 443-444页

作者：杜风华包钢第三职工医院儿科内蒙古包头014010

新生儿持续肺动脉高压（pphn）是指生后肺血管阻力持续性增高,肺动脉压超过体循环动脉压,临床以严重低氧血症为主要表现,多见于足月儿或过期产儿。当有高碳酸血症、低氧血症、代谢性酸中毒、循环量减少、心功能不全及低体温等情况时.

关键词： pphn 26 持续肺动脉高压肺血管阻力严重低氧血症高频振动体循环动脉压过期产儿平滑肌增生肺动脉压心功能不全

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Safety in treatment: Classical pharmacotherapeutics and new avenues for addressing maternal depression and anxiety during pregnancy

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PHARMACOLOGICAL REVIEWS 2025年第3期77卷 100046页

作者： Dagher, Merel Cahill, Catherine M. Andrews, Anne M. Univ Calif Los Angeles Semel Inst Neurosci & Human Behav Hatos Ctr Neuropharmacol Dept Psychiat & Biobehav Sci 635 Charles E Young Dr South Los Angeles CA 90095 USA Univ Calif Los Angeles Neurosci Interdept Program Los Angeles CA USA Univ Calif Los Angeles Dept Chem & Biochem Los Angeles CA USA Univ Calif Los Angeles Calif NanoSyst Inst Los Angeles CA USA

We aimed to review clinical research on the safety profiles of antidepressant drugs and associations with maternal depression and neonatal outcomes. We focused on neuroendocrine changes during pregnancy and their effects on antidepressant pharmacokinetics. Pregnancy-induced alterations in drug disposition and metabolism impacting mothers and their fetuses are discussed. We considered evidence for the risks of antidepressant use during pregnancy. Teratogenicity associated with ongoing treatment, new prescriptions during pregnancy, or pausing medication while pregnant was examined. The Food and Drug Administration advises caution regarding prenatal exposure to most drugs, including antidepressants, largely owing to a dearth of safety studies caused by the common exclusion of pregnant individuals in clinical trials. We contrasted findings on antidepressant use with the lack of treatment where detrimental effects to mothers and children are well researched. Overall, drug classes such as selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors appear to have limited adverse effects on fetal health and child development. In the face of an increasing prevalence of major mood and anxiety disorders, we assert that individuals should be counseled before and during pregnancy about the risks and benefits of antidepressant treatment given that withholding treatment has possible negative outcomes. Moreover, newer therapeutics, such as ketamine and K-opioid receptor antagonists, warrant further investigation for use during pregnancy. Significance Statement: The safety of antidepressant use during pregnancy remains controversial owing to an incomplete understanding of how drug exposure affects fetal development, brain maturation, and behavior in offspring. This leaves pregnant people especially vulnerable, as pregnancy can be a highly stressful experience for many individuals, with stress being the biggest known risk factor for developing a mood or a

关键词： ACTH adrenocorticotropic hormone AMPA α -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid BDNF brain-derived neurotrophic factor CRH corticotropin-releasing hormone CYP cytochrome P FST forced swim test GH growth hormone HPA hypothalamic-pituitary-adrenal 5HT serotonin IR immediate-release KOR κ opioid receptor MAOI monoamine oxidase inhibitor NAS neonatal adaptation syndrome NET norepinephrine transporter NSF novelty suppressed feeding NMDA N -methyl- d -aspartate pphn persistent pulmonary hypertension RCT randomized controlled trial SERT serotonin transporter SNRI serotonin norepinephrine reuptake inhibitor SSRI selective serotonin reuptake inhibitor TCA tricyclic antidepressant TRD treatment-resistant depression TST tail suspension test Vd volume of distribution YLD year lived with disability

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Sildenafil Attenuates Persistent Pulmonary Hypertension of the Newborn via Inhibiting the Growth and Migration of Pulmonary Artery Smooth Muscle Cells

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JOURNAL OF SURGICAL RESEARCH 2025年 306卷 249-256页

作者： Kang, Lili Han, Yujie Liu, Chen Liu, Xianghong Li, Xiaomei Li, Zilong Li, Xiaoying Shandong Univ Childrens Hosp Dept Neonatol 23976 Jingshi Rd Jinan 250022 Shandong Peoples R China

Introduction: Sildenafil, a selective phosphodiesterase 5 inhibitor, modulates vascular dysfunction, with hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) proliferation, migration, and invasion closely implicated in vascular remodeling in persistent pulmonary hypertension of the newborn (pphn). This study aimed to assess sildenafil's protective effects against pphn and elucidate underlying molecular pathways. Methods: Cell Counting Kit-8, wound healing, and Transwell assays evaluated rat PASMC proliferation, migration, and invasion under hypoxia. A rat pphn model assessed sildenafil's impact on right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH), and vascular remodeling. JAK2/STAT3 signaling was analyzed via Western blotting. Results: Sildenafil significantly inhibited hypoxia-induced PASMC proliferation, migration, and invasion. In addition, sildenafil reduced RVSP, RVH, and vascular remodeling in pphn. Further, sildenafil decreased JAK2 and STAT3 phosphorylation in hypoxia-exposed PASMCs and the pphn rat model. The JAK2/STAT3 pathway agonist colivelin reversed sildenafil's suppressive effects on PASMC proliferation, migration, invasion, as well as RVSP, RVH, and vascular remodeling in pphn. Conclusions: Sildenafil protects against pphn by inhibiting PASMC proliferation, migration, and invasion via suppression of JAK2/STAT3 signaling, indicating its potential as a therapeutic target for pphn and contributing to a more comprehensive understanding of pphn pathogenesis.

关键词： Invasion JAK2 Migration PASMCs pphn Proliferation Sildenafil STAT3

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Circulating Intercellular Adhesion Molecule as a Novel Marker of Pulmonary Hypertension in Newborn

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INDIAN PEDIATRICS 2025年 1-3页

作者： AbdelMassih, Antoine Fakhry ElAnwary, Sherif Taha, Nourhan Radwan, Noha AbouDeif, Mahmoud Othman Cairo Univ Cairo Univ Children Hosp Fac MedPediat Cardiol Div Dept PediatPediat Cardiol Unit Kasr Al Ainy St Cairo 12411 Egypt Cardiac Sci Dept Pediat Cardiol Div Sheikh Khalifa Med City Abu Dhabi U Arab Emirates Cairo Univ Cairo Univ Children Hosp Dept Pediat Neonatol Unit Cairo Egypt Cairo Univ Fac Med MD Pediat Training Program Cairo Egypt Cairo Univ Fac Med Clin & Chem Pathol Dept Cairo Egypt

BackgroundIntercellularAQ1 adhesion molecules (ICAMs) are released from the endothelium in response to shear stress. Their role in persistent pulmonary hypertension (pphn) remains *** neonates (30 pphn, 30 controls) underwent serum ICAM testing and *** and left ventricular function was depressed in pphn cases. Tricuspid annular plane systolic excursion was reduced (Cases 8 +/- 1 vs. Controls 11 +/- 3.5). ICAM was elevated in cases (332 +/- 96 vs. 208 +/- 36).ConclusionICAM is a sensitive pphn marker. Elevated ICAM may result from endothelial damage or contribute to pphn pathogenesis. Further studies are needed to confirm these results and explore this relationship.

关键词： Right ventricular systolic pressure Hypoxia pphn Respiratory distress in newborn

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欧盟评估抗抑郁药引起pphn风险

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临床合理用药杂志 2010年第16期3卷 64-64页

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