High-Dose Oral Ibuprofen in Treatment of Patent Ductus Arteriosus in Full-Term Neonates

Background:

Patent ductus arteriosus (PDA) is an important risk for heart failure due to left to right shunt in term neonates.

Objectives:

In this study, we evaluated the effect of high dose ibuprofen in closure of PDA in term neonates.

Patients and Methods:

We used double dose ibuprofen (20 mg/kg, 10 mg/kg, and 10 mg/kg) for 3 - 30 day old term neonates with PDA who were admitted in the neonatal wards of Shiraz University of Medical Sciences. The results of this study were compared to the data of the previous study in our center which used the low dose of ibuprofen (10 mg/kg, 5 mg/kg, and 5 mg/kg).

Results:

29 full term neonates received high-dose ibuprofen, in 18 neonates, PDA was closed after 4 days (62.1% versus 43.3% for the standard dose and 4.7% for the control group in the previous study) (P = 0.001). The results showed no significant correlation between the closure rate and gestational age, postnatal age, sex, and weight. In the 4^th day of treatment, size of the pulmonic end of ductus arteriosus decreased from 2.09 mm to 0.77 mm compared to 1.68 mm to 0.81 mm in the standard dose of oral ibuprofen and 2.1 mm to 1.4 mm in the control group (P = 0.046).

Conclusions:

This study indicated that high-dose oral ibuprofen was more effective in closing or decreasing the size of PDA.     

动脉导管未闭患儿介入治疗前后血浆N末端脑利钠肽水平及心功能变化

目的应用心脏超声技术及检测血浆N末端脑利钠肽（NT-proBNP）水平,探讨经皮动脉导管未闭（PDA）封堵术对心功能影响。方法PDA患儿55例,术前按照小儿心衰改良Ross标准分为无心衰组31例,轻度心衰组14例,中重度心衰组10例（重度心衰1例）。选择年龄、体质量相匹配健康儿童15例作为健康对照组。应用酶联免疫吸附法测定血浆NT-proBNP水平。同时测定左室舒张末期容量指数（LVEDVI）、左室收缩末期容量指数（LVESVI）、左室射血分数（LVEF）、左室缩短分数（LVFS）等反映心室功能及负荷的超声心动图指标。结果1.PDA患儿术前LVEDVI、LVESVI均显著高于健康对照组（Pa〈0.01）,且各组间随着心功能严重程度增加而显著升高（P〈0.01）。2.术前血浆NT-proBNP水平随着心功能严重程度增加而升高,中重度心衰组高于轻度心衰组（P〈0.01）,轻度心衰组高于无心衰组（P〈0.01）,无心衰组与健康对照组比较无统计学差异（P〉0.05）。3.PDA患儿术后3个月血浆NT-proBNP水平、LVEDVI、LVESVI均较术前显著降低（Pa〈0.01）,接近健康对照组水平（P〉0.05）。4.血浆NT-proBNP水平与LVESVI（r=0.653P〈0.01）、LVEDVI（r=0.741P〈0.01）呈正相关,而与LVEF、LVFS等无显著相关性（P〉0.05）。结论PDA堵闭术后3个月在临床症状和反映左室功能超声指标明显改善同时,术前高血流动力学负荷对心室细胞影响也逐渐恢复。     

Long-Term Results of Transcatheter Closure of Patent Ductus Arteriosus in Infants Using Amplatzer Duct Occluder

Objective

Patent ductus arteriosus (PDA) is one of the most frequently seen congenital heart diseases. Its closure is recommended because of the risk of infective endocardis, as well as morbidity and mortality in the long. The aim of this study was to assess the long term results of the transcatheter closure of PDA in infants using amplatzer duct occlude (ADO).

Methods

From May 2004 to September 2011, forty eight infants underwent transcatheter closure of PDA. A lateral or right anterior oblique view aortogram was done to locate PDA and to measure its size. Before discharge, repeat aortogram was performed to evaluate eventual residual shunt and to confirm the appropriate deployment of the ADO. Follow up evaluations were done with transthoracic echocardiography at discharge, 1 month, 6 months, 12 months and yearly thereafter.

Findings

The mean age of patients at procedure was 9.18±2.32 (range 3 to 12) months, mean weight 6.73±1.16 (range 4.5 to 10.1) kg. The PDA occluded completely in 20 out of the 48 patients. Twenty four patients had trivial or mild shunt and two patients had moderate residual shunt which disappeared in one patient within 24 hours and other patient with moderate shunt in 1 month. One patient (age 8 months) had mild LPA stenosis. The device emobolization occurred in two patients, immediately after the procedure in one and during night in the other patient

Conclusion

The long term results suggested that transcatheter closure of PDA using Amplatzer duct occluder is a safe and effective treatment in infants less than 1 year of age with minimal complications.     

Usefulness of Indomethacin for Patent Ductus Arteriosus in Full-Term Infants

The aim of this retrospective study was to evaluate the effectiveness of indomethacin therapy for patent ductus arteriosus (PDA) in full-term infants. The patients were 41 full-term infants with a PDA birth weight (BW) > or =2500 g and a gestational age (GA) > or =37 weeks. The echocardiographic evaluation and medical management of PDA in these infants was similar to that for PDA in low-birth-weight infants. Indomethacin (0.2-0.25 mg/kg/dose) was given intravenously at 12-24-hour intervals within 23 days of birth. Of the 41 infants, 12 showed complete closure, and 13 showed improvement of clinical symptoms. These 25 infants were classified as the responder group (61%). The other 16 infants, who did not show improvement in clinical symptoms, were classified as the nonresponder group. Statistical analysis revealed no difference between the two groups regarding GA, BW, Apgar score at 1 minute, minimum diameter of the DA before treatment, the average age at the initiation of treatment, and DA flow pattern. No severe adverse reactions were observed in any infant. Indomethacin therapy appears to be an effective medical treatment option for PDA in full-term symptomatic infants prior to considering surgical treatment.     

Myocardial Contractility in Premature Neonates With and Without Patent Ductus Arteriosus

Controversy exists as to whether a hemodynamically significant left-to-right shunt due to a patent ductus arteriosus (PDA) affects ventricular contractility. Load-dependent indices such as ejection fraction and shortening fraction have traditionally been used to assess contractility, but the relationship between the rate-corrected velocity of fiber shortening (MVCFc) and wall stress may be more suitable, as it is a preload-independent, afterload-adjusted method of assessing ventricular contractility. Age-related differences have been established for these variables in normal adults and children and it has been recommended for use in the premature neonate. The study was performed to assess left ventricular contractility in premature neonates with a significant left-to-right shunt due to a PDA. Using echocardiography, we measured the relationship of MVCFc to stress at peak systole (SPS) in two groups of premature infants. Group 1 consisted of 15 controls (680–1495 g, 25–32 weeks gestation), and Group 2 of 15 neonates with hemodynamically significant PDA (840–1635 g, 26–33 weeks gestation). In both groups, MVCFc was linearly and inversely related to SPS (p < 0.001). The regression equations were as follows: Group 1, MVCFc = –0.0153SPS + 1.70 (R² = 0.68); and Group 2, MVCF = – 0.019SPS + 1.89 (R² = 0.76). There was no significant difference in the relationship between the two groups, but their slopes were significantly steeper and had a higher Y-intercept than the relationship we previously reported for older children. This preliminary study establishes the normal MVCFc/SPS relationship in the premature neonate (25–33 weeks gestation) and suggests that premature infants function at a higher resting contractile state than older children. A hemodynamically significant PDA has no effect on contractility. These data will be useful in assessing left ventricular contractility in premature neonates with other types of ventricular loading and noncardiac stress.     

急性心力衰竭患儿血浆脑钠素及心钠素水平的变化

目的探讨急性心力衰竭患儿血浆脑钠素(BNP)及心钠素(ANP)水平变化及其意义。方法选择不同病因的充血性心力衰竭(CHF)患儿46例及肺炎患儿40例、先天性心脏病患儿31例、健康儿童40例,应用酶联免疫吸附法分别检测血浆BNP及ANP水平,用多普勒超声心动图测量心力衰竭患儿心衰期及恢复期心脏指数(CI)及左室射血分数(LVEF)。结果CHF患儿心衰前期BNP即开始升高,心衰时达高峰(P<0.001),恢复期BNP水平渐下降,但仍高于正常值(P<0.001);心衰时心脏CI、LVEF均明显下降(P<0.01);CHF患儿心衰时升高的BNP水平与CI、LVEF均呈明显负相关(r=-0.61,0.79P均<0.05);同时测定的ANP动态变化趋势与BNP类似;CHF患儿心衰时的BNP/ANP比值远远高于正常对照;心衰时BNP与ANP异常率比较有显著差异(P<0.05);心衰时BNP水平与LVEF、CI值相关性优于ANP。结论CHF患儿血清BNP及ANP水平明显升高.且与心衰程度关系密切,BNP反映心脏功能改变较ANP更敏感,更具有特异性。     

Transient Dynamic Subaortic Stenosis in Premature Neonates After Patent Ductus Arteriosus Ligation

We describe 2 premature infants with PDA that did not respond to medical therapy and required surgical ligation. Both infants developed transient dynamic subaortic obstruction that resolved without specific therapy. This may have occurred due to sudden changes in the left ventricular volume.     

Cerebral and Abdominal Arterial Hemodynamics in Preterm Infants with Patent Ductus Arteriosus

Using Doppler echocardiography we evaluated the effect of ductal shunt flow on the cerebral and abdominal arterial blood flow in 25 preterm infants. Eligible for inclusion in this study were healthy preterm newborn infants. They were divided into two groups based on their gestational age: group A, 33-36 weeks (15 infants) and group B, 28–32 weeks (10 infants). Two-dimensional Doppler echocardiograms were obtained in each infant during the first 8 hours of life and repeated every 6–12 hours until no ductal shunt flow could be detected. Flow in the ductus arteriosus, the basilar artery and the coeliac artery were examined. Closure of the ductus arteriosus occurred significantly later(p< 0.05) in group B than in group A. Pulsatility indices of flow in the basilar and coeliac arteries were high when the ductus was patent, decreasing to a fixed level with closure. This study suggests that a shunt of the patent ductus arteriosus (PDA) adversely influences the cerebral and abdominal blood flow in preterm infants.     

The Physiological and Biological Significances of Human Atrial Natriuretic Peptide in Neonates

ABSTRACT. The purpose of our study was to analyze the physiological and biological significances of the high human atrial natriuretic peptide (hANP) levels during early post-natal period. The absolute values or changes of plasma hANP concentrations did not correlate with the absolute values or changes of body weight, blood pressure, urinary sodium/creatinine and urinary aldosterone/creatinine ratios. Gel permeation chromatography of samples from two neonates revealed the presence of two molecular forms of hANP, α and β, both in the plasma and urine. In the plasma, the β-hANP was predominant on the 3rd day of life and the α-hANP on the 6th day of life. The change from one form to another was independent of the absolute value of hANP. We obtained no evidence suggestive of a physiological role of the high plasma hANP concentration during the early post-natal period. However, because of biological differences between these two fractions, their distribution must be taken into account when attempting to interpret the high hANP values observed in neonates.     

N端脑钠肽前体对新生儿心力衰竭的早期诊断价值

目的检测血浆N端脑钠肽前体(NT-proBNP)在高危新生儿心力衰竭(HF)的表达水平,探讨NT-proBNP对新生儿HF的早期诊断价值。方法收集窒息后HF新生儿35例(HF组)及同期无窒息、无HF新生儿20例(对照组)。于出生第2天、第7天用电化学发光法检测血浆NT-proBNP水平,质量法检测CK-MB水平,采用SPSS16.0软件进行统计学分析。结果与对照组比较,治疗前HF组NT-proBNP、CK-MB水平均高于对照组,差异有统计学意义(P<0.05,0.01);治疗后CK-MB水平仍显著高于对照组(P<0.05),而NT-proBNP水平与对照组比较差异无统计学意义(P>0.05)。与治疗前比较,HF组治疗后NT-proBNP、CK-MB水平均显著降低,差异有统计学意义(P<0.05,0.001);治疗前后对照组CK-MB水平差异无统计学意义(P>0.05),NT-proBNP水平显著降低(P<0.01)。结论联合检测NT-proBNP、CK-MB水平可动态观察心肌损害程度及HF恢复情况,NT-proBNP检测可作为临床早期诊断新生儿HF的指标之一。     

Influence of Dopamine on Atrial Natriuretic Peptide Level in Premature Infants

ABSTRACT. The role of dopamine (DA) in the activation and/or release of atrial natriuretic peptide (ANP) was investigated in 11 premature infants during the early postnatal period. Mean plasma concentration of ANP and free DA level before DA infusion was 252.6±210 fmol/ml, and 0.4±0.2 ng/ml, respectively. DA infusion in a dose of 2μg/kg/min caused a rise in plasma free DA level to 59.7±21.5 ng/ml and a significant increase in GFR, diuresis, sodium excretion and fractional sodium excretion. The plasma concentration of ANP, however, remained unchanged (252.6±210.0 vs. 213±143.0 fmol/ml). Thus, our data failed to demonstrate a stimulatory effect of DA on ANP release in premature infants. The role of the high plasma concentration of ANP in preterm neonates immediately after birth has to be clarified.     

血浆脑利钠肽对扩张性心肌病患儿病情的评估

目的探讨脑利钠肽(BNP)与扩张性心肌病患儿病情严重程度的相关性。方法扩张性心肌病患儿30例为研究组,选择健康儿童30例为对照组。两组均测定血浆BNP水平。进行t检验,比较各组血浆BNP水平,采用直线相关分析法分析BNP值与左室射血分数和心功能分级关系。结果扩张性心肌病患儿血浆BNP水平明显高于对照组[(429.4±270.2)ng/Lvs(67.0±10.2)ng/L];扩张性心肌病患儿血浆BNP水平与心功能分级呈正相关(r=0.950P<0.01),与左心室射血分数呈负相关(r=-0.695P<0.001),与左心室舒张末期内径无明显相关性(r=0.030P>0.1)。受试者工作特征曲线(ROC)曲线下面积为0.550,以血浆BNP水平95ng/L为判定心衰界值时,具有较高的灵敏度、特异度。结论血浆BNP可作为迅速评估扩张性心肌病患儿病情的依据之一。     

急性充血性心力衰竭患儿血浆脑利钠肽变化的意义

目的通过测定急性充血性心力衰竭(CHF)患儿血浆脑利钠肽(BNP)水平的变化,进一步确定其临床应用价值。方法BNP测定采用酶标法;选择住院CHF患儿48例,其中肺炎心衰36例,先天性心脏病心衰12例。正常对照组40例。分别进行CHF组不同时期BNP水平与正常对照组比较,探讨CHF患儿心功能参数变化并与BNP水平作相关分析。根据NYHA小儿CHF分级,进行不同心功能级别CHF患儿BNP比较。结果CHF患儿心衰期及恢复期BNP水平显著高于正常对照组(t=14.30,20.38 P均<0.01);CHF患儿心衰期CI、LVEF值与正常对照组比较有显著差异(t=8.85,12.62 P均<0.01),恢复期CI及LEVF值与正常对照组比较差异无显著(t=1.62,1.64 P均>0.05),提示心衰时心功能有明显的改变。同时心衰患儿BNP与CI、LVEF数值均呈负相关(r=-0.61,-0.79 P均>0.05);心功能分级不同,BNP水平明显不同,心衰程度越重,BNP水平愈高,差异有显著性(P均<0.01)。结论心衰时BNP水平明显增高,确定BNP在CHF诊断中价值。并与动态心功能变化密切相关;心衰程度越重,血BNP水平越高。BNP可作为评价心功能程度及预后,指导临床治疗的指标。     

脑钠肽在新生儿持续肺动脉高压诊断和治疗中的意义

目的 探讨脑钠肽(BNP)在新生儿持续肺动脉高压(PPHN)诊断和治疗中的临床应用价值,明确BNP是否可以作为判别PPHN的生化定量指标.方法 采用前瞻性对照研究,对54例发绀患儿及时行心脏彩色超声Doppler检查,结合临床鉴别出PPHN组29例、non-PPHN组25例,以同期住院无发绀患儿12例作为对照组.应用免疫荧光分析测定66例患儿血清BNP水平,比较各组患儿间BNP水平差异,应用SPSS 13.0统计软件描绘ROC曲线,评价该方法的价值及寻找判断PPHN的最佳临界值.结果 PPHN组新生儿BNP水平[(1 937.40±1 392.36) ng·L-1]显著高于non-PPHN组新生儿[(537.00±731.49) ng·L-1]和对照组[(50.72±36.50) ng·L-1](F=19.42,P<0.001),而non-PPHN和对照组BNP水平比较无统计学意义(P>0.05);ROC曲线下面积为0.903,95%可信区间0.818～0.988;判别PPHN的最佳BNP水平为807 ng·L-1,以此为标准,判别PPHN的灵敏度为0.828,特异度为0.880.结论 PPHN新生儿血清BNP水平明显升高,而BNP可作为一种动态观察指标,在判别PPHN的发生及指导合理治疗、判断预后中有重要临床意义.     

Brain Natriuretic Peptide Levels in Pediatric Cancer Patients with Febrile Neutropenia

Brain natriuretic peptide (BNP) is considered as a prognostic marker in patients with sepsis, but no data are available on BNP in pediatric cancer patients with febrile neutropenia (FN). Twenty-five pediatric cancer patients with FN were included in this study. Serum BNP level was measured. The mean BNP level was 330.8 ± 765.3 pg/mL (5.9–3806 pg/mL). BNP levels of 12 patients were found over the normal level. High BNP levels were related to some conditions of the patients, and these were statistically significant (P < .05). These conditions were required erythrocyte suspension, had pneumonia, time stayed in hospital, and neutropenia time. When regression test was done, required erythrocyte suspension for anemia and had pneumonia were found to be statistically significant. In conclusion, this is one of the first studies on BNP levels in pediatric cancer patients with FN. However, further studies with large sample sizes are needed to confirm the results and provide new data about this issue.     

心力衰竭婴儿血浆脑利钠肽水平变化的意义

目的探讨心力衰竭(HF)婴儿血浆脑利钠肽(BNP)水平变化与HF严重程度的关系,及其对婴儿HF诊断、心功能分级和疗效监测的临床意义。方法随机选取2006年10月-2008年9月在本院儿科住院的HF婴儿30例为研究对象,并根据Ross分级标准将其分成轻、中、重度3组。在HF纠正前后收集HF婴儿血浆,检测BNP水平。随机选取本院体检中心健康婴儿30例为健康对照组。健康对照组和HF组婴儿血浆BNP水平测定采用化学发光微粒子免疫分析法;采用M型超声心动图测量HF组婴儿的左心室射血分数(LVEF),并分析血浆BNP水平与LVEF的相关性。结果HF婴儿血浆BNP水平[(629.17±508.53)×10-6ng.L-1]显著高于健康对照组[(65.13±31.98)×10-6ng.L-1](t=4.884,P<0.05)。HF程度越重,血浆BNP水平升高越显著,血浆BNP水平与LVEF呈负相关(r=-0.508,P<0.05),与心功能分级呈正相关(r=0.527,P<0.01)。HF纠正后血浆BNP水平[(105.02±57.81)×10-6ng.L-1]显著低于HF纠正前[(629.17±508.53)×10-6ng...     

Utility of N-Terminal Brain Natriuretic Peptide Plasma Concentrations in Comparison to Lactate and Troponin in Children with Congenital Heart Disease Following Open-Heart Surgery

We conducted a prospective study in a pediatric cardiac intensive care unit in order to determine the diagnostic value of N-terminal brain natriuretic peptide (N-BNP) plasma concentration in the perioperative care of children with congenital heart disease (CHD). N-BNP plasma concentrations were determined by using a validated enzyme immunoassay. We measured N-BNP the day before surgery and up to 15 days postoperatively in 23 children (age range, 0.25–11 years) undergoing cardiac surgery due to various CHDs. Supply and duration of catecholamines, vasodilators, and respiratory therapy were determined and correlated to N-BNP. In addition, troponin T (TnT) and arterial Lactat (aL) concentrations were measured simultaneously. We found a significant correlation between preoperative and maximal N-BNP levels and dosage of vasodilators (r = 0.41, p < 0.02 and r = 0.83, p < 0.01, respectively). Maximal TnT and aL levels were not correlated to dosage of vasodilators. The dosage and duration of catecholamines, the duration of respiratory therapy, and the plasma concentration of TnT and aL were not correlated to pre- or perioperative N-BNP. Maximal TnT and aL levels were correlated to duration (r = 0.53, p < 0.01 and r = 0.48, p < 0.02) and dosage (r = 0.52, p < 0.02 and r = 0.60, p < 0.01) of catecholamines and duration of respiratory therapy (r = 0.57, p < 0.01 and r = 0.50, p < 0.02). As recent studies show, N-BNP appears to be a powerful neurohumoral indicator of ventricular function and prognosis for guiding therapy in the outpatient department or for discriminating cardiac from noncardiac symptoms. In contrast, the value of N-BNP for guiding perioperative therapy in pediatric cardiac intensive care units is limited.