Cardiac catheterization in children with pulmonary arterial hypertension

Cardiac catheterization of childhood pulmonary arterial hypertension (PAH) is used to assess the severity of the disease as well as prognosis, selection of the most adequate pulmonary vasodilators, and evaluation of effectiveness. Sudden deterioration of cardiovascular hemodynamics, however, can be easily induced by pain, patient agitation, catheter manipulation, and by vasodilator provocation tests; these could trigger a pulmonary hypertension crisis, vagotony, respiratory distress, and hemoptysis resulting in critical complications, including death. Those patients with New York Heart Association functional class IV are at an especially high risk. It is noteworthy that pulmonary arteriography is a contraindication in patients with PAH. In a review of 7218 adult patients, 76 (1.1%) serious complications, including four deaths, were reported; with regard to the pediatric patients, 29 (10.7%) out of 270 patients with complications, including one with cardiogenic shock requiring cardiopulmonary resuscitation in addition to minor complications, were reported. To prevent serious complications, basic and routine precautions, such as oxygen and concomitant transcutaneous oxygen saturation and electrocardiogram monitoring during transportation to and from the catheter laboratory, are mandatory. Furthermore, the cooperation of experienced physicians and well informed medical staff in addition to meticulous preparation, for example, calculation of prior doses of catecholamine and confirmation of the presence of emergency equipment, is required.     

Medulloblastoma in children 0-3 years old: forty years' experience in slovenia

Twenty-one children 0-3 years with MB were admitted 1960-1996, of 14 before treated 1984, 3 had no treatment, 5 had postoperative RT, one had radioactive gold IT. Seven treated 1986-1996 had preradiation Cht, 5 with HDCy. Of the 14 treated before 1984, 12 died within 1 year, one after 42 years in hypopharynx cancer, one is alive, of normal height and working. Of the 7 treated 1986-1996, 3 with disseminated disease died. Four are longtime survivors, 2 treated with reduced doses of RT of normal development. Preradiation Cht with HDCy and reduced doses of RT seems to be a reasonable approach.     

Pharmacokinetics of sildenafil in children with pulmonary arterial hypertension

Background

Recently, sildenafil was introduced to treat pulmonary arterial hypertension (PAH); however, there are currently few studies on the pharmacokinetics of sildenalfil in children. Therefore, we aimed to carry out a pharmacokinetic study of sildenafil in children with PAH using a single dose.

Methods

Twelve children diagnosed with PAH, consisting of with ten males and two females, were recruited for the study after obtaining written consent from their parents or guardians. Blood samples were obtained predose and at 0.25, 0.5, 1, 2, 4, 8 and 12 hours after the oral administration of 1 mg/kg of sildenafil using an extemporal pediatric formulation developed in our laboratory. The samples were analyzed using a previously validated high performance liquid chromatography method.

Results

A pharmacokinetic analysis using the WinNonlin 3.1 program that considered the Akaike information criterion (AIC) for selecting a more adjustable model was performed. The following pharmacokinetic parameters were obtained: maximal concentration (C_max): 366±179 ng/mL, time to maximal concentration: 0.92±0.30 hours, elimination half-life (t_1/2): 2.41±1.18 hours, total clearance (CL_tot/F): 5.85±2.81 L/hour, volume of distribution (Vd/F): 20.13±14.5 L, absorption rate constants (Ka): 0.343 hour^–1, elimination rate (Ke): 0.35 hour^–1, area under curve from zero to infinity: 2061±618 ng/mL/hour. The data of all patients adjusted to the model of one compartment were corroborated using AIC.

Conclusions

The parameters Ka, Ke and t_1/2 were found to be similar to those reported in adults; however, the values of C_max and Vd/F were significantly higher. Based on these findings, we propose that treatment regimen of sildenafil be adjusted in children with PAH.

     

西地那非在儿童肺动脉高压的应用现状

西地那非(sildenafil)用于治疗男性勃起功能障碍的一线药,具有里程碑意义.近些年相关研究已证实西地那非通过选择性抑制5型磷酸二酯酶(PDE5),该酶是肺动脉血管中主要的磷酸二酯酶,抑制该酶可使环磷酸鸟苷(cGMP)维持在较高水平,后者促进内源性一氧化氮(NO)的血管扩张作用,具有治疗肺动脉高压(PAH)的功效.     

儿童特发性肺动脉高压的急性肺血管扩张试验

目的 探讨儿童特发性肺动脉高压(IPAH)患者急性肺血管扩张试验的指征、方法学.方法 2009年10月到2011年6月收治的WHO心功能Ⅱ～Ⅲ级的IPAH患儿参与了该项研究.在右心导管检查获取了基线血流动力学资料后,从中心静脉泵入腺苷,起始剂量为50 μg/(kg·min),每2分钟递增25 μg/(kg·min),直至达到最大剂量250μg/(kg·min)或达到阳性反应.结果 15例IPAH患儿纳入了该项研究,平均年龄为6.3岁,平均肺动脉压(mPAP)为(67.1±15.9)mm Hg (1 mm Hg =0.133 kPa),肺毛细血管楔压(PCWP)为(9.7±2.9) mm Hg,肺血管阻力指数(PVRI)为(17.9±7.5) Wood U·m2.在急性肺血管扩张试验中,3例mPAP下降幅度超过10 mm Hg,并且绝对值≤40 mm Hg,为阳性反应;另外12例为阴性反应.15例中有5例在试验中出现不良反应,包括胸闷不适(n=1)、体循环低血压(n=3)、心动过缓(n=1).停用腺苷后30～60 s,上述不良反应均迅速消失.结论 静脉用腺苷是一种安全、有效的肺血管扩张剂,可作为儿童IPAH患者急性肺血管扩张试验的试验药物.     

Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: open-label pilot study

Abstract:  Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs. In addition, our previous studies suggested that autologous EPC transplantation was feasible, safe, and might have beneficial effects on exercise capacity and pulmonary hemodynamics in adults with IPAH. Thus, we hypothesized that transplantation of EPCs would improve exercise capacity and pulmonary hemodynamics in children with IPAH. Thirteen children with IPAH received intravenous infusion of autologous EPCs. The right-sided heart catheterization and 6-MWD test were performed at baseline and at the time of 12 wk after cell infusion. At the time of 12 wk, mPAP decreased by 6.4 mmHg from 70.3 ± 19.0 to 63.9 ± 19.3 mmHg (p = 0.015). PVR decreased by approximately 19% from 1118 ± 537 to 906 ± 377 dyn s/cm⁵ (p = 0.047). CO increased from 3.39 ± 0.79 to 3.85 ± 0.42 L/min (p = 0.048). The 6-MWD increased by 39 m from 359 ± 82 to 399 ± 74 m (p = 0.012). NYHA functional class also improved. There were no severe adverse events with cell infusion. The small pilot study suggested that intravenous infusion of autologous EPCs was feasible, safe, and associated with significant improvements in exercise capacity, NYHA functional class, and pulmonary hemodynamics in children with IPAH. Confirmation of these results in a randomized controlled trial are essential.     

儿童特发性肺动脉高压的临床特点及预后的影响因素

目的：调查儿童特发性肺动脉高压( idiopathic pulmonary arterial hypertension,IPAH)的临床特点及预后的影响因素,为临床诊治及预后评估提供参考。方法回顾性分析2006年1月至2015年12月于我科诊断为IPAH患儿的临床资料,根据预后分为存活组和死亡组,对相关指标应用Logistic回归分析筛选出影响IPAH患儿预后的危险因素。结果共计26例患儿纳入研究,存活组17例,死亡组9例。儿童IPAH以学龄期儿童多见,平均年龄(6.6±3.6)岁,男女比例1.17∶1。所有患儿均有活动耐力下降和乏力症状,晕厥及呼吸困难、水肿的发生率分别为34.6％及23.1％,肺动脉瓣听诊区第2心音亢进为最常见体征(92.3％),50.0％患儿在诊断时心功能为Ⅲ~Ⅳ级。超声心动图检查示肺动脉收缩压(PASP)平均(79.0±20.3) mmHg(1 mmHg＝0.133 kPa),16例患儿右心室重度扩大。心电图以ST-T改变及右心室高电压最为常见,血浆脑钠肽(BNP)平均浓度为(870.4±720.9) pg/ml。单因素分析显示晕厥(OR＝26.25,95％CI 3.04~226.60,P＝0.003),心功能Ⅲ~Ⅳ级(OR＝19.199,95％CI 1.88~196.53,P＝0.0128),PASP≥70 mmHg(OR＝9.936,95％CI 1.81~∞,P＝0.005),BNP≥850 pg/ml(OR＝59.991,95％CI 4.69~767.62,P＝0.002)是预后不良的危险因素。结论儿童IPAH临床少见,预后不良。晕厥、心功能分级、PASP程度及BNP浓度是儿童IPAH预后的重要影响因素。 BNP作为IPAH的标志物在病情程度评估以及预后预测中具有一定的参考价值。     

Persistent pulmonary hypertension of the newborn with transposition of the great arteries: successful treatment with bosentan

Persistent pulmonary hypertension of the newborn (PPHN) occurs in 1–4% of neonates with transposition of the great arteries with intact ventricular septum (TGA/IVS). This association is often lethal. To our knowledge, only eight survivors have been described in the literature, two of whom benefited from extracorporeal membrane oxygenation (ECMO). We report two cases of PPHN complicating a TGA/IVS that were refractory to multiple therapies and resolved 48 hours after initiation of bosentan therapy. Bosentan, an oral dual endothelin-1 receptor antagonist, is a new treatment for pulmonary arterial hypertension that was both effective and safe in these two cases of TGA/IVS with PPHN. To our knowledge, it is the first use of bosentan in newborns.     

先天性门体静脉分流相关性肺动脉高压5例临床分析

目的探讨儿童先天性门体静脉分流相关性肺动脉高压(PAH-CPS)的临床特点。方法回顾分析2012年1月至2019年1月收治的PAH-CPS患儿的临床资料。结果共5例患儿,男2例、女3例,初诊年龄0.08～4.4岁。主要表现为反复肺部感染、肝脾大、肝功能异常、肺动脉高压。超声心动图检查明确患儿均有不同程度肺动脉高压、合并心内畸形。腹部超声示肝内外门体静脉分流。腹部增强CT和心导管造影可显示肝内外血管的走形和发育。结论 PAH-CPS可表现为反复肺部感染、肝脾肿大、肝功能异常等;超声检查可提供诊断线索,腹部增强CT扫描、心导管造影可明确诊断。     

Detection of pulmonary arterial morphology in tetralogy of Fallot with pulmonary atresia by computed tomography: 12 years of experience

Our aim was to evaluate the feasibility of using computed tomography (CT) to define the pulmonary artery anatomy in patients with tetralogy of Fallot and pulmonary atresia (TOF-PA). We retrospectively reviewed 110 patients with TOF-PA between 1995 and 2008. Those who received cardiac catheterization and surgery within 3 months of their CT examinations were enrolled. Based on Dr. Somerville's classification, the pulmonary arterial pattern was determined, including identifiable pulmonary trunk (type I), the presence of both left and right pulmonary arteries without trunk (II), only left or right pulmonary artery present (III), and absent intrapericardial pulmonary arteries (IV). The accuracy of both imaging modalities was evaluated with operation findings as the golden standard. The effective radiation doses and adverse events were also recorded. In the 64 eligible patients (median age, 23 months), CT and catheterization demonstrated accurate pulmonary arterial morphology in 60 (60/64) and 53 (53/64) TOF-PA patients, respectively. Thirty-two of 35 type I patients were correctly identified by CT, whereas 26 were correctly identified by catheterization (p?=?0.03). Of the 20 type II TOF-PA patients, 19 were diagnosed by CT, whereas 18 were diagnosed by catheterization. CT and catheterization both successfully defined six type III and three type IV patients. The median calculated radiation doses caused by CT and catheterization were 4.5 and 5.6 mSv, respectively (p?>?0.05). CONCLUSIONS: For patients with TOF-PA, CT could accurately delineate pulmonary arterial morphology with the same level of accuracy as cardiac catheterization. Therefore, CT can be considered a reasonable diagnostic alternative for such patients.     

Follow-up of 5- to 11-year-old children treated for persistent pulmonary hypertension of the newborn

Aim: Determine the prevalence of sensorineural hearing loss (SNHL) and relate this to cumulative exposure to hypoxia, hypocapnia and hypotension. Describe chronic health problems among 5- to 11-year-old children treated for persistent pulmonary hypertension of the newborn (PPHN).
Methods: The index group consisted of 85 children and a reference group was matched for age, sex and municipality of current residence. Questionnaires were sent to the families. The families in the index group were asked to participate in an examination of their child's hearing.
Results: Seven children (11%) had SNHL. SNHL was not associated with hypoxia, hypocapnia or hypotension during treatment for PPHN. In the index group chronic health problems were reported in 42% compared with 17% in the reference group (chi-square test, p = 0.001). Twenty-one percent in the index group were treated with bronchodilator therapy compared with 8% in the reference group (chi-square test, p = 0.028). In the index group five children had cerebral palsy and two had developmental delay. Nineteen percent in the index group and 5% in the reference group had remedial education (chi-square test, p = 0.008).
Conclusion: Children treated for PPHN are at high risk for SNHL. Exposure to hypoxia, hypocapnia or hypotension did not predict SNHL. The incidence of chronic health problems and use of remedial education was high.     

Neonatal resuscitation training program in Malaysia: results of the first 2 years

OBJECTIVES: To determine the number of providers and instructors trained by the initial 37 core instructors during the first 2 years following the launch of the Malaysian Neonatal Resuscitation Program (NRP). To identify remediable problems which interfered with the propagation of the NRP in Malaysia. METHODOLOGY: A prospective observational study carried out over a 2-year period between 2 September 1996 to 2 September 1998. For every training course conducted, the instructors completed a NRP course report form (Form A) that documented the instructors involved in the course. For every participant who attended the course and successfully completed it, the instructors submitted a record form (Form B) that contained the name, hospital address, department, profession, place of work, language used for training and the marks obtained by the individual participant. After each course, completed forms A and B were returned to the NRP secretariat for compilation. RESULTS: Of the 37 core instructors, 35 (94.6%) carried out training courses in their respective home states. A further 513 new instructors and 2256 providers were trained subsequently. A total of 2806 health personnel from all 13 states of Malaysia were NRP-certified during the first 2 years. However, 61.2% (n = 335) of the 550 instructors were inactive trainers, having trained less than four personnel per instructor a year. Most of the NRP-certified personnel were either doctors (32.0%) or nursing staff (64.4%). More than 60% of these worked either in the labour rooms, neonatal intensive care units or special care nurseries. At least one person from all three university hospitals and all general hospitals, 89.3% (92/103) of the district hospitals, 3.5% (73/2090) of the maternal and child health services, and 21% (46/219) of the private hospitals and maternity homes, were trained in the NRP. CONCLUSION: Dissemination of the NRP in Malaysia during the first 2 years was very encouraging. Further efforts should be made to spread the program to private hospitals and the maternal and child health services. In view of the large number of inactive instructors, the criteria for future selection of instructors should be more stringent.     

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目的 探讨雾化吸入伊洛前列素进行急性血管扩张试验的价值.方法 研究对象为2007年2月至2008年5月在广东省心血管病研究所住院的50例先天性心脏病合并肺动脉高压患儿,对所有患儿进行左右心导管检查,之后肺动脉内注射酚妥拉明或雾化吸入伊洛前列素进行急性血管扩张试验,试验后重复左右心导管检查.根据Fick公式计算血流动力学参数.综合判断肺动脉高压性质,将惠几分成两组:动力组和梗阻组.动力组患儿进行手术治疗,术后定期随访并修正术前诊断.结果 酚妥拉明会显著增高受试者的心率,而伊洛前列素对心率的影响较轻微;酚妥拉明和伊洛前列素都能够降低平均肺动脉压力和肺血管阻力,升高肺循环血流量;酚妥拉明同时会降低平均主动脉压力和体循环阻力,升高体循环血流量,而伊洛前列素对体循环没有明显的影响.在使用伊洛前列素的急性血管扩张试验中,平均肺动脉压力、肺血管阻力/体循环阻力和肺循环血流量/体循环血流量等参数的变化在动力组和梗阻组中差异无统计学意义(P值分别为0.016、0.024和0.030).而使用酚妥拉明的急性血管扩张试验中,平均肺动脉压力和肺血管阻力两项参数的变化在动力组和梗阻组中差异有统计学意义(P值分别为0.017和0.004).结论 在先天性心脏病合并肺动脉高压的患儿中,使用酚妥拉明或伊洛前列素进行急性血管扩张试验都能够有效区分动力性与梗阻性肺动脉高压.酚妥拉明用药前后,肺循环和体循环的压力、阻力和血流量都有明显变化.而伊洛前列素雾化吸入以影响肺循环为主,可以保持相对平稳的血流动力学,在安全性上优于酚妥拉明.     

Thyroid gland volume and urinary iodine excretion in children 6-11 years old in an endemic area

Goiter prevalence and urinary iodine excretion levels were assessed in 605 schoolchildren (301 males and 304 females), aged 6-11 years, living in the Antalya region, a well known endemic goiter area in Turkey. Goiter prevalence was evaluated by clinical examination and ultrasound of the thyroid gland. Urinary iodine levels were expressed as microg/g creatinine. Goiter by inspection and palpation was found in 35% (n = 212) of all subjects, in 37.5% (n = 114) of girls and 32.5% (n = 98) of boys. Iodine deficiency of moderate degree was detected from the point of goiter prevalence. With regard to the upper limits of reference thyroid volumes reported by WHO and ICCIDD, goiter by ultrasonography was found in 34% (n = 206) of all subjects, in 36.8% (n = 112) of girls and 31% (n = 94) of boys. Median iodine/creatinine ratios of all subjects, and goitrous and non-goitrous subjects, were 64.1+/-20.1, 62.8+/-21.8 and 64.9+/-19.1 microg/g, respectively. Urinary iodine excretion levels revealed mild iodine deficiency in the region. No significant correlation was observed between urinary iodine excretion levels and thyroid volumes (r = 0.12, p>0.05). Iodine deficiency of mild to moderate degree in schoolchildren aged 6-11 years was detected in Antalya. It was concluded that urgent measures must be undertaken to eradicate iodine deficiency in the region.     

Psychophysiological factors in high intellectual potential: comparative study in children aged from 8 to 11 years old]

Factors of intellectual talent as well as physiological and psychological characteristics are little known. However, giftedness is now a social problem and the knowledge of precocity hallmarks should permit the diagnosis in order to undertake the adequate educational orientation of these children. From questionnaires given anonymously to parents, this work showed comparative results between a population of gifted children and a control one. OBJECTIVES: The aim of this study was to present precocity hallmarks in the gifted population, following factorial analysis of socio-economic and familial parameters, as well as medical and psycho-physiological variables linked with the children's post-natal life. POPULATION: Four hundred and twelve children aged eight to 11 years, from Lyon, have been used in the survey: 217 children (control group) were included after a random selection in schools, and 195 children (gifted group, IQ >130, Wechsler test) were enrolled after clinician's diagnoses in four medical departments. RESULTS: Regression analysis allowed to draw relation between several factors and giftedness: abnormal pregnancy (CR =3.205, P =0.009), perinatal stress (CR =2.166, P =0.003), and presence of migraine (CR =3.169, P =0.001). Parents living together (married or not) (CR =2.100, P =0.080) with a good and superior level of learning (CR =5.464, P =0.0002) were also linked with giftedness. CONCLUSION: Our results indicate that precocity hallmarks are multifactorial. These data confirm some socio-economic and medical physiological features correlated with giftedness, and suggest that psychological factors may bear on the etiology of intellectual talent. We focus on the hypothesis than early stress may play a role on central nervous system maturation in these children.     

CT of the chest in the evaluation of idiopathic pulmonary arterial hypertension in children

Background Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease in children. By definition it is a diagnosis of exclusion, and CT of the chest is primarily performed to exclude other causes. Previous studies have defined CT features suggestive of the diagnosis of IPAH, but these have all been limited to the adult population. Objective Contrast-enhanced chest CT and high-resolution CT findings in IPAH were evaluated in an attempt to define features consistently seen in children with this condition. Materials and methods The chest CT scans performed at initial presentation were reviewed in 17 children with echocardiographic or angiographic evidence of IPAH. Result There were nine boys and eight girls, ranging in age from 1 month to 17 years. The extrapulmonary findings included cardiomegaly with right-sided cardiac enlargement, which was seen in 13 children. The central pulmonary arteries were enlarged in 15 children, with peripheral enlargement in two. In six children this resulted in bronchial compression. In addition, mediastinal and hilar lymphadenopathy was noted in three children. Prominent intrapulmonary features included a peripheral vasculopathy, with enlarged tortuous vessels, seen in eight children. Ill-defined ground-glass centrilobular opacities were also noted in eight children, representing the most common parenchymal abnormality. Other findings included septal lines in five, diffuse ground-glass opacification in four and focal hyperlucent zones in three. Mosaic attenuation was seen in one child. Conclusion A variety of imaging findings are identified in IPAH. Features particularly consistent with the diagnosis include peripheral vasculopathy and centrilobular opacities in the setting of cardiomegaly and central pulmonary arterial enlargement.