西地那非治疗新生儿持续肺动脉高压比对研究(英文)

目的 探讨西地那非治疗新生儿持续肺动脉高压的疗效与安全性.方法 2005年1月至2008年10月收治持续肺动脉高压患儿45例,其中男25例,女20例;平均胎龄(39.3±2.4)周;平均出生体重(3 114.0±10.2)g;人院时平均年龄(13.0±0.8)h.病例随机分为西地那非、妥拉苏林和米力农治疗3组.应用超声心动仪检测肺动脉压力.结果 45例患儿中治愈30例,好转6例,无效9例,总有效率80.0%;西地那非、妥拉苏林和米力农3组患儿的治疗有效率比较,差异无统计学意义;3组患儿治疗前后平均肺动脉压力下降,差异有统计学意义;3组组间比较差异无统计学意义.所有患儿在治疗过程中均未见不良反应.结论 西地那非对新生儿持续肺动脉高压具有良好治疗效应,可有效降低平均肺动脉压力,改善心功能.     

米力农治疗婴幼儿先天性心脏病并肺动脉高压的疗效观察

目的 探讨米力农治疗婴幼儿先天性心脏病(CHD)并肺动脉高压 (PAH)的临床疗效及血流动力学、心功能指标的变化和意义.方法 选择广西壮族自治区人民医院2004年7月-2007年7月收治的45例婴幼儿CHD并PAH患儿.随机分为米力农治疗组(米力农组,n=25)及多巴胺加酚妥拉明治疗组(多巴胺组,n=20).米力农组予米力农0.5 μg /(kg·min);多巴胺组予多巴胺和酚妥拉明,均为5 μg/(kg·min).二组均持续静脉给药5 d,观察临床疗效、血流动力学和心功能指标变化,并进行比较.结果 米力农组用药后5 d,患儿临床症状、体征好转,血流动力学及心功能指标较治疗前显著改善(Pa<0.05),总有效率为92.0%;多巴胺组治疗前后血流动力学及心功能指标改善不明显(Pa>0.05),总有效率为75.0%.米多农组与多巴胺组治疗后临床疗效、血流动力学和心功能指标比较差异均有统计学意义(Pa<0.05).米力农组患儿心率、血压较治疗前均无显著变化(Pa>0.05),无严重心律失常发生.结论 米力农具有正性肌力和扩血管的作用,对肺血管床有选择性扩张作用,能明显改善CHD婴幼儿并PAH的心功能,降低其肺动脉压力,不影响其血压和心率,其临床疗效优于多巴胺.     

手控呼吸囊正压通气治疗新生儿持续肺动脉高压的临床研究

目的 探讨手控呼吸囊正压通气治疗新生儿肺动脉高压的疗效.方法 在机械通气治疗新生儿呼吸衰竭时,出现肺动脉高压,通过调节呼吸机参数及药物治疗后,血氧饱和度仍低于85%的患儿,通过多普勒超声确诊为新生儿持续肺动脉高压20例,将其分为2组,对照组继续呼吸机治疗.调整呼吸机参数,观察组则用新生儿呼吸囊(带压力表)接气管导管正压通气,吸入氧浓度1.0,呼吸频率60～80次/min,吸气峰压30～35 cm H2O(1 cm H2O=0.098 kPa),治疗期间监测肺动脉压力,当肺动脉收缩压≤75%体循环收缩压时,PaO2维持在80 mm Hg(1 mm Hg=0.133 kPa)左右,血氧饱和度大于95%持续2 h,重上呼吸机治疗.对照组及观察组药物治疗相同.结果 观察组治疗总有效率为63%,对照组总有效率为11%,差异有显著性(P＜0.05).结论 手控呼吸囊正压通气治疗新生儿持续肺动脉高压,有一定疗效,方法简便、安全.     

小剂量硝酸甘油联合酚妥拉明持续静脉滴注治疗新生儿肺动脉高压的疗效

目的 探讨小剂量硝酸甘油联合酚妥拉明持续静脉滴注治疗新生儿肺动脉高压(PAH)的疗效.方法 2000年6月-2006年12月经超声心动图检查证实存在PAH的新生儿178例为研究对象.随机分为对照组85例,治疗组93例.其中先天性心脏病或肺结构异常42例(对照组20例,治疗组22例);其他病因所致者136例(对照组65例,治疗组71例).患儿经皮测血氧饱和度(TcSaO2)均低于85%.对照组予综合治疗加酚妥拉明0.2～0.3 mg/(kg·min),按10μg(kg·min)的速度泵入,1次/d,连用3 d;治疗组在此基础上加用硝酸甘油,0.3～0.5 μg/(kg·min),连续泵入6 h,若无效每天递增0.3～0·5μg/(kg·min),最多应用7 d.所有患儿治疗前后进行临床表现、心率、呼吸、血压、TeSaO:及平均肺动脉压(MPAP)监测.结果 治疗组总有效率、MPAP及平均TeSaO2治疗前后与对照组比较差异均有显著性(Pa<0.05),其中二组其他病因患儿比较差异亦有非常显著性(Pa＜0.01).不同病因、不同MPAP治疗前后比较也有显著性差异(Pa<0.05).治疗组体循环血压均无明显变化.结论 小剂量硝酸甘油联合酚妥拉明持续静脉滴注治疗PAH新生儿疗效优于单独应用酚妥拉明,且无严重不良反应.     

新生儿持续性肺动脉高压治疗的临床证据

目的 评价治疗新生儿持续性肺动脉高压(PPHN)措施的有效性和安全性,为临床应用提供指导.方法 通过数据库检索出符合纳入分析条件的相关文献9篇,采用Meta分析方法 进行定性、定量综合分析.得出合并优势比(OR)及其95%可信区间.结果 目前尚无随机病例对照试验(randomized controlledtrial,RCT)对过度通气、高频通气、控制性碱血症、扩血管药物(硫酸镁、妥拉苏林、前列腺素与前列环素、米力农)肺表面活性物质、治疗PPHN的临床效果进行评价;口服西地那非可降低PPHN患儿的氧合指数(OI)(P<0.01),降低住院期间患儿的病死率(P<0.05);iNO治疗PPHN后30～60min可显著升高患儿的动脉血氧分压(P<0.00001)、减少使用体外膜肺(ECMO)(P<0.00001),长期神经系统的发育随访和对照组比较差异无统计学意义(P>0.05);成本-效果分析吸入一氧化氯(iNO)治疗PPHN,每个患儿多花费1141美元,增量成本-效果比为33 234美元;ECMO治疗PPHN可减少住院期间新生儿病死率(P<0.05),患儿1岁时神经系统发育和对照组比较差异无统计学意义(P>0.05).结论 iNO可显著升高患儿的动脉血氧分压,ECMO治疗可减少患儿的病死率,但增加治疗成本;口服西地那非治疗PPHN疗效评价的随机对照实验(RCT)样本量较少,需要进一步加大样本量.对传统治疗PPHN的措施应进行设计严格、多中心、大样本的RCT.     

米力农对先天性心脏病并肺动脉高压及心力衰竭患儿的术前干预作用

目的 探讨米力农对小儿先天性心脏病(CHD)并肺动脉高压(PAH)及心力衰竭(CHF)术前治疗的效果.方法 收集2006年1月-2008年7月上海交通大学附属儿童医院ICU收治的CHD患儿40例.年龄1个月～3岁.均为左向右分流型CHD,并PAH及CHF.将患儿随机分为研究组与对照组,各20例,二组病种、年龄、心功能及PAH程度比较无显著性差异.二组患儿均应用强心、利尿及扩血管治疗,另外,研究组20例加米力农静脉维持[0.5 μg/(kg·min)],对照组20例加多巴胺和多巴酚丁胺各5μg/(kg·min)静脉维持.分别于用药前、静脉维持用药72 h及停药后2 h通过彩色多普勒超声心动图检测二组各项心脏收缩、舒张功能及肺动脉压力指标.结果 研究组用药72 h各项心脏收缩功能指标(心脏指数、左室射血分数及左事短轴缩短率)和舒张功能指标(左室收缩时间间期、右室收缩时间间期及二尖瓣E峰和A峰比值)均显著优于对照组(Pa<0.05),肺动脉压力下降程度显著高于对照组(P<0.05);研究组改善心功能有效率显著高于对照组(P<0.05).结论 米力农对CHD并PAH及CHF患儿具有正性肌力和扩血管作用,能明显改善心功能和降低肺动脉压力,为手术纠正心脏畸形提供良好时机.     

一氧化氮吸入治疗新生儿持续肺动脉高压

】　目的　探讨吸入一氧化氮（NO）对新生儿持续肺动脉高压（PPHN）的治疗效果。方法　对6例窒息后PPHN进行NO吸入治疗，入院后经呼吸机支持，应用NO前呼吸机吸入氧浓度平均为0.93±0.10，平均气道压力为(12.7±2.7)cm H     

肺动脉高压新生儿血浆硫化氢变化的意义

目的 探讨肺动脉高压新生儿血浆硫化氢(H2S)的变化及其与肺动脉高压(PH)相关性,为临床有效治疗新生儿PH提供新的思路和理论依据.方法 随机选取2005年3月-2006年3月本院ICU病房住院PH新生儿16例,选取同期住院非PH新生儿16例作为对照组.对全部研究对象均行超声心动图检查,依据简化柏努力方程AP=4V2max计算出压力阶差,估测三尖瓣二侧压力,间接判断其肺动脉压,对二组新生儿于出生3～10 d清晨8:00取静脉血4 mL,迅速分离其血浆,采用敏感硫电极法测定其血浆H2S水平,应用氨基酸分析仪测定其同型半胱氨酸水平.应用SPSS 10.0软件进行t检验.结果 PH新生儿肺动脉收缩压为4.27～9.73(6.49.±1.79)kPa;对照组肺动脉收缩压正常.肺动脉高压组血浆同型半胱氨酸及H:s水平明显高于对照组[(11.94 ±6.65)μmol/Lvs(6.43 ±2.08)μmol/L,t=2.630 P=0.016;(26.99 ±1.33)μmol/Lvs(24.92 ±1.36)μmol/L,t=4.373 P=0].结论 PH新生儿血浆同型半胱氨酸和H2S明显升高,内源性H2S上调可能参与肺动脉压力的调节.H2S可能通过扩张肺动脉降低肺动脉压力而对PH具有保护作用.     

吸入伊洛前列素对先天性心脏病患儿术后肺动脉高压的治疗作用

目的 评价吸入伊洛前列素对先天性心脏病术后肺动脉高压的疗效,并初步探讨其机制.方法 以中国医学科学院阜外心血管病医院小儿心脏中心PICU收治的体外循环下双心室矫治手术后合并肺动脉高压13例患儿为研究对象,在术后48 h内常规治疗的基础上,给予有效剂量伊洛前列素25 ng/(kg·min),每次吸入10 min,每4小时1次.观察患儿的血流动力学改变,采用酶联免疫吸附法检测血浆cAMP和cGMP浓度.结果 13例患儿平均年龄(17.88±12.56)个月,平均体质量(9.29±3.59)kg.治疗前右房压、肺动脉收缩压、肺动脉收缩压/主动脉收缩压比值分别是(11.5±1.41)mm Hg(1 mm Hg=0.133 kPa)、(61.64±13.6)mm Hg和0.66±0.16;治疗后20 min分别降至(9.88±1.88)mmHg、(47.67±12.18)mm Hg和0.52±0.15;治疗前后差异均有显著性(P＜0.01).治疗后120 min伊洛前列素疗效仍然存在.治疗前患儿血浆cAMP浓度为(335.75±127.31)μg/L,治疗后20 min升至(519.68±148.54)μg/L,治疗前后差异有显著性(P＜0.01).治疗前后血压、呼吸机条件和血浆cGMP浓度没有明显变化(P＞0.05).结论 对于先天性心脏病术后合并肺动脉高压患儿,吸入伊洛前列素可以显著降低肺动脉压力、改善肺循环血流动力学状态,可能与增高血浆cAMP浓度有关系.吸入伊洛前列素对体循环和呼吸功能影响小,未观察到明显不良反应.     

一氧化氮吸入联合高频振荡通气治疗新生儿肺动脉高压疗效分析

目的探讨一氧化氮吸入(i NO)联合高频振荡通气(HFOV)治疗新生儿持续肺动脉高压(PPHN)的临床疗效。方法回顾性分析2010年1月至2013年12月本院新生儿重症监护病房收治的PPHN患儿临床资料,根据不同时间段治疗措施不同分为HFOV组、常频机械通气(CMV)+i NO组、HFOV+i NO组。记录并比较各组患儿治疗前、治疗2、12、24 h的吸入氧浓度(Fi O2)、氧合指数(OI)、肺动脉压力,以及呼吸机使用情况、住院时间、症状变化及转归。结果治疗2、12、24 h,HFOV+i NO组Fi O2、OI、肺动脉压力均低于CMV+i NO组和HFOV组,CMV+i NO组低于HFOV组[2 h Fi O2:(0.43±0.15)比(0.58±0.11)、(0.71±0.13),OI:(17.1±5.6)mm Hg比(20.3±6.2)mm Hg、(22.6±6.4)mm Hg,肺动脉压力:(46.2±4.6)mm Hg比(51.3±4.4)mm Hg、(58.3±3.7)mm Hg;24h Fi O2:(0.26±0.14)比(0.32±0.16)、(0.42±0.13),OI:(8.4±4.2)mm Hg比(11.6±4.6)mm Hg、(13.8±3.8)mm Hg,肺动脉压力:(15.3±4.4)mm Hg比(24.5±4.5)mm Hg、(35.6±3.6)mm Hg,P<0.05]。HFOV+i NO组机械通气时间、氧疗时间及住院时间均短于CMV+i NO组和HFOV组,CMV+i NO组短于HFOV组,差异有统计学意义(P<0.05);各组患儿病死率及Ⅲ度以上颅内出血发生率差异无统计学意义(P>0.05)。结论早期i NO联合HFOV治疗PPHN疗效显著,能迅速改善肺动脉高压患儿的氧合情况,显著缩短患儿的上机时间、氧暴露时间及住院时间,但对患儿病死率及Ⅲ度以上颅内出血发生率没有影响。     

Cerebral blood flow during treatment for pulmonary hypertension.

AIM: To determine if the haemodynamics of systemic and cerebral circulation are changed during treatment for persistent pulmonary hypertension of the newborn (PPHN). METHODS: Fifteen term newborn piglets with hypoxia induced pulmonary hypertension were randomly assigned either tolazoline infusion (Tz), hyperventilation alkalosis(HAT), and inhaled nitric oxide (iNO). Mean pulmonary arterial pressure (PAP), mean systemic arterial pressure (SAP), and cerebral blood flow volume (CBF) were measured. RESULTS: During hypoxic breathing, PAP increased significantly in all groups. After treatment PAP decreased significantly in all groups, but no significant difference was observed between groups. SAP decreased significantly only in the Tz group, and CBF reduced significantly only in the HAT group. On the other hand, iNO did not change SAP or CBF. CONCLUSION: Inhaled NO might be ideal for the resolution of pulmonary hypertension.     

Endotracheal tolazoline: pharmacokinetics and pharmacodynamics in dogs

Tolazoline is a potent vasodilator of both arteries and veins and has a powerful effect on the pulmonary vasculature, reducing hypoxic pulmonary vasoconstriction and lowering pulmonary artery pressure. Intravenous tolazoline lowers the mean pulmonary arterial pressure and resistance and increases the cardiac index when given to infants with persistent pulmonary hypertension of the newborn (PPHN). Endotracheally administered tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endotracheal tolazoline in order to determine the relationship between endotracheal tolazoline administration, plasma concentration and its effects on the cardiovascular and respiratory systems. Tolazoline was administered endotracheally to 7 newborn dogs, and its serum concentration and the haemodynamic parameters were monitored for 270 min post-delivery. Results are expressed as median and quartiles. It was found that 15 s after dosing, tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 2.64 (1.36; 13.16) microg/ml. The extent of tolazoline absorption was 305 (148;453) microg/ min/ml. The volume of distribution was 3.4 (1.6;7.4) 1/kg. The total body clearance was 12.1 (10.9;23.9) ml/min/kg and the elimination half-life was 225 (171;303) min. Endotracheal tolazoline produced an initial short-lived decrease in mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endotracheal tolazoline significant tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. A single endotracheal dose of tolazoline is effectively absorbed and produces measurable pharmacological effects. Determining the optimal endotracheal dose of tolazoline in the clinical setting requires additional evaluation.     

The management of neonatal pulmonary hypertension

Most neonates with clinically significant pulmonary hypertension (PH) will have either persistent PH of the newborn (PPHN) or bronchopulmonary dysplasia. Cyanotic congenital heart disease must be actively ruled out as part of the differential diagnosis of PPHN. The maintenance of ductal patency with prostaglandins E1 or E2 in cases of doubt is safe and potentially beneficial given their pulmonary vasorelaxant properties. Specific tools in the treatment of PPHN include modern ventilatory strategies, inhaled nitric oxide, sildenafil, prostacyclin and extracorporeal membrane oxygenation. Rarely will a cardiac lesion be primarily responsible for neonatal PH although pulmonary vein stenosis and the persistence of an arterial duct must be considered, particularly in the older preterm baby with bronchopulmonary dysplasia.     

Plasma cyclic guanosine monophosphate reflecting the severity of persistent pulmonary hypertension of the newborn

The aim of the study was to examine the relationship between the plasma concentration of cyclic guanosine monophosphate (cGMP) and pulmonary pressure and hypoxia defined by oxygenation index (OI) in newborn infants with severe persistent pulmonary hypertension (PPHN) on inhaled nitric oxide (NO). In this prospective study, 18 newborn infants having Doppler ultrasound-diagnosed PPHN and treated with NO were investigated. The ratio of pulmonary artery to systemic artery pressure (PAP/SAP) and OI was assessed before treatment and at 0.5, 1, 12, and 24 h from the beginning of NO. At these time points, plasma concentrations of cGMP could be determined in 11 patients. The association of birth asphyxia as assessed by Apgar 1 min and 5 min and plasma cGMP before the NO treatment was examined. The initial median plasma concentration of cGMP was 37.3 pmol/ml (IQR 13.3-79.6). After the start of NO, cGMP increased significantly within 60 min (p = 0.003) and peaked at 12 h. Initial plasma cGMP was associated with Apgar score (1 and 5 min). OI decreased within 30 min of NO and PAP/SAP within 60 min. Persistent high PAP/SAP after 1 h of NO was associated with low cGMP concentration (r = 0.70, p = 0.02). We conclude that a significant increase in plasma cGMP is already evident after 60 min of NO therapy. This effect is accompanied by changes in oxygenation index and in pulmonary artery pressure. Initial plasma concentrations of cGMP were associated with hypoxia assessed as Apgar score.     

Pulmonary microthrombi syndrome in newborn infants with unresponsive persistent pulmonary hypertension

Some newborn infants with either primary or secondary persistent pulmonary hypertension (PPHN) remain hypoxemic, hypercarbic, and acidotic despite therapeutic efforts. In autopsies of 23 infants who had PPHN, diffuse platelet-fibrin thrombi were present in the pulmonary microcirculation of eight (15.2 +/- 18.1 thrombi/cm2 lung tissue) and absent in 15 (0.2 +/- 0.3 thrombi/cm2 lung tissue), (P less than 0.004). Diagnoses in group A (thrombi) were pneumonia and sepsis (four patients), meconium inhalation (3), and primary PPHN (1); and in group B (no thrombi) pneumonia and sepsis (4), meconium inhalation (4), primary PPHN (4), hyaline membrane disease (2), and diaphragmatic hernia (1). The only significant differences between the two groups were the response to tolazoline infusion as assessed by changes in partial pressure of arterial oxygen (PaO2) and the platelet counts. Group A responded less favorably to tolazoline (14.8 mm Hg vs 83.6 mm Hg; P less than 0.05) and had lower platelet counts (51,000/microliter vs 128,000/microliter) (P less than 0.01) than group B. No significant differences could be detected in Apgar scores, duration or mode of mechanical ventilation, oxygen requirements, arterial blood gas tensions or pH, systemic arterial blood pressure, coagulation profile, amount of blood product transfusions, or intravascular catheter use. Pulmonary microthrombi should be added to the list of mechanisms for PPHN and may explain why some infants do not respond well to therapeutic efforts aimed at vasodilation. Thrombocytopenia and failure to respond to pulmonary vasodilators might suggest the diagnosis.     

Sildenafil reverses hypoxic pulmonary hypertension in highland and lowland newborn sheep

Perinatal exposure to chronic hypoxia induces sustained hypertension and structural and functional changes in the pulmonary vascular bed. We hypothesized that highland newborn lambs (HLNB, 3600 m) have a higher pulmonary arterial pressure (PAP) due in part to a higher activity/expression of phosphodiesterase 5 (PDE5). We administered sildenafil, a PDE5 inhibitor, during basal and hypoxic conditions in the pulmonary hypertensive HLNB and compared them to lowland newborn lambs (LLNB, 580 m). Additionally, we compared the vasodilator responses to sildenafil in isolated small pulmonary arteries and the PDE5 mRNA expression and evaluated the vascular remodeling by histomorphometric analysis in these newborn lambs. Under basal conditions, HLNB had a higher PAP and cardiac output compared with LLNB. Sildenafil decreased the PAP during basal conditions and completely prevented the PAP increase during hypoxia in both groups. HLNB showed a greater contractile capacity and a higher maximal dilation to sildenafil. PDE5 mRNA expression did not show significant differences between HLNB and LLNB. The distal pulmonary arteries showed an increased wall thickness in HLNB. Our results showed that HLNB are more sensitive to sildenafil and therefore could be useful for treatment of pulmonary hypertension in high-altitude neonates.     

Extralobar sequestration with congenital diaphragmatic hernia: a complicated case study

This article presents a case study of an infant (JG) with an antenatal diagnosis of a left diaphragmatic hernia and an extralobar sequestration of his right lung, which was noted postnatally. JG's course was complicated by persistent pulmonary hypertension of the newborn (PPHN) and suspected pulmonary hypoplasia, and he required support with extracorporeal life support (ECLS). JG's case was unusual in his presentation of extreme PPHN that was unresponsive to inhaled nitric oxide and ECLS. His PPHN was nearly intractable, requiring treatment with vasodilators combined with intravenous sildenafil, which had never been tried in our institution before this case. The article concludes with a discussion of the etiology, diagnosis, and management of congenital diaphragmatic hernia and extralobar sequestration, singly and in combination.     

Treatment of persistent pulmonary hypertension of the newborn

OBJECTIVE: To review the medical literature, emphasizing the new scientific advances in the treatment of persistent pulmonary hypertension of the newborn. SOURCES: Literature review using Medline and Cochrane library. SUMMARY OF THE FINDINGS: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by an increase in pulmonary vascular resistance associated with right to left shunt through the foramen ovale or ductus arteriosus, leading to marked hypoxemia and respiratory failure. The balance between the vasoconstrictor (endothelin) and vasodilator (nitric oxide and prostaglandin I2) mediators plays an important role in the regulation of the transition from fetal circulation with high pulmonary vascular resistance to postnatal circulation with low pulmonary vascular resistance. In addition to general management, cardiovascular support, the treatment of the cause of the PPHN, and the use of selective pulmonary vasodilator such as inhaled nitric oxide (iNO) are indicated. Furthermore, the combined therapy with iNO and high-frequency oscillatory ventilation significantly improved the oxygenation of patients who were refractory to iNO therapy and conventional ventilation. The practice of hyperventilation and the administration of nonspecific pulmonary vasodilators (tolazoline) should be avoided. On the other hand, the administration of surfactant to patients with PPHN due to meconium aspiration should be considered. However, if all these therapies fail, extracorporeal membrane oxygenation (ECMO) should be considered as rescue therapy. CONCLUSIONS: The mortality due to PPHN has significantly decreased with the use of new therapies, and the major concern today is the quality of life of these patients, especially in terms of neuropsychomotor development.     

Combination therapy for life-threatening pulmonary hypertension in a premature infant: first report on bosentan use

Premature infants with preterm premature rupture of membranes (PPROM) are at high risk of severe respiratory failure because of lung hypodysplasia associated with persistent pulmonary hypertension of the newborn (PPHN). We describe the clinical course of a 28-week gestation infant with PPROM from the 20th week and prolonged oligohydramnios before delivery, who developed refractory hypoxia treated with oral bosentan as adjunct therapy to inhaled nitric oxide (iNO) and oral sildenafil. Conclusion Our experience suggests that bosentan can be used in the premature infant with PPHN after PPROM. To the best of our knowledge, this is the first report of bosentan treatment in a premature infant.