Effect of patent ductus arteriosus and indomethacin treatment on serum cardiac troponin T levels in preterm infants with respiratory distress syndrome

Cardiac troponin T (cTnT) represents a sensitive and specific marker of ischemic myocardial damage in adult and neonatal populations. The aim of this study was to detect the potential ischemic effect of persistent patent ductus arteriosus (PDA) and indomethacin treatment on the coronary vascular bed by measuring cTnT concentrations. cTnT levels were measured in 23 preterm infants (<32 weeks of gestational age) with respiratory distress syndrome (RDS), 11 with PDA and 12 without, at 2, 4, and 7 days after birth. cTnT concentrations (mean ± SEM) significantly decreased (P < 0.05) from the 2nd (0.63 ± 0.09 μg/l) and the 4th (0.77 ± 0.13 μg/l) to the 7th postnatal day (0.28 ± 0.04 μg/l). At day 2 after birth, cTnT levels in preterm infants with RDS were significantly higher (P < 0.05) than our reference values for healthy preterm neonates (0.63 ± 0.09 μg/l vs 0.18 ± 0.04 μg/l). No differences were found between RDS infants with and without PDA at 2 (0.65 ± 0.13 vs 0.61 ± 0.14 μg/l), 4 (0.71 ± 0.21 vs 0.87 ± 0.16 μg/l), and 7 (0.26 ± 0.05 vs 0.29 ± 0.07 μg/l) days of life. In infants with PDA, cTnT levels did not differ before the first dose of indomethacin was given (0.65 ± 0.14 μg/l) or 2 h (0.65 ± 0.15 μg/l) and 48 h (0.71 ± 0.21 μg/l) afterwards. Conclusion In preterm infants with RDS the occurrence of PDA and indomethacin treatment are not associated with ischemic cardiac damage as detected by cTnT measurements. Received: 23 December 1998 and in revised form: 4 May 1999 / Accepted: 11 October 1999     

Early treatment of patent ductus arteriosus in premature infants with severe respiratory distress syndrome

Summary In 1983, a US National Collaborative Study (NCS) proposed criteria for the diagnosis of hemodynamically significant patent ductus arteriosus (PDA) in premature infants with respiratory distress syndrome (RDS), but the widespread use of pulsed Doppler cross-sectional echocardiography (PD-CSE) in neonatal intensive care units has made direct assessment of the ductus possible thus providing more timely therapy. We have compared the results in 30 premature infants with severe RDS, assessed according to the guidelines of the US NCS, with those in 51 infants whose PDA was diagnosed by PD-CSE. Together with a significant reduction in the age at treatment (7.8±3.9 vs 2.4±1.1 days), there was a reduced dependence on artificial ventilation (14.8±11.0 vs 7.8±2.7 days), a reduction in the number requiring surgical ligation of PDA (9 vs 2), a decreased incidence of bronchopulmonary-dysplasia (BPD) (40% vs 16%), and a reduction of unfavorable outcome of treatment (death or BPD) (76% vs 49%).     

Indomethacin and cerebral blood flow in premature infants treated for patent ductus arteriosus

Central blood flow (CBF) was estimated by an intravenous 133-xenon technique in six preterm infants before and after administration of indomethacin for closure of patent ductus arteriosus. CBF fell in all infants (range 12%–40%), the mean fall was 24% (P<0.005). Though none of the infants showed signs of impaired cerebral function during or following the injections, the results do not indicate whether or not the use of indomethacin is a potential hazard.Abbreviations PDA patent ductus arteriosus - CBF cerebral blood flow - PaCO₂ arterial carbon dioxide tension - MAP mean arterial blood pressure     

Cardiocirculatory effects of patent ductus arteriosus in extremely low-birth-weight infants with respiratory distress syndrome

BACKGROUND: Cardiocirculatory effects of hemodynamically significant patent ductus arteriosus (hsPDA) have not been systematically studied in extremely low-birth-weight (ELBW) infants with respiratory distress syndrome (RDS). The objective of the present study was to evaluate the effects of hsPDA on the left ventricular output (LVO) and organ blood flows in ELBW infants with RDS. METHODS: Extremely low-birth-weight infants (birth-weight <1000 g) treated with surfactant for RDS were studied by serial Doppler flow examinations. Doppler flow variables in 19 infants in whom hsPDA developed (hsPDA group) were compared with those in 19 infants without hsPDA matched for gestational age, birth-weight, and postnatal age (non-hsPDA group). All infants in the hsPDA group had pharmacologic closure of ductus arteriosus when hsPDA developed. RESULTS: Before pharmacological closure of PDA, the hsPDA group had significantly higher LVO, lower blood flow volume of the abdominal aorta, and lower mean blood flow velocities in the celiac artery, superior mesenteric artery, and renal artery than the non-hsPDA group. These alterations in the hsPDA group reverted to the levels in the non-hsPDA group after the closure of PDA and had no deleterious effects on the cardiorespiratory status. No significant differences between the groups were found in mean blood flow velocities of the anterior cerebral artery throughout the study period. CONCLUSION: These results indicate that although LVO is increased, the splanchnic and renal blood flows are decreased when hsPDA develops in ELBW infants with RDS. The effects of these alterations of LVO and organ blood flows on the cardiorespiratory course seem to be minor when early pharmacologic closure of PDA is done.     

不同治疗方式对早产儿动脉导管未闭的疗效及安全性评价

目的 探讨早产儿动脉导管未闭(PDA)的临床治疗方式及效果,总结手术治疗PDA 的经验。方法 2013 年1 月至2014 年12 月诊断为PDA 并行手术治疗的早产儿19 例为手术组,同期未行手术治疗的19 例PDA 早产儿为非手术组。分析两组在病史因素、临床因素、病死率及主要并发症等方面的差异,同时从术前准备及手术结果方面分析手术治疗的特点及临床效果。结果 非手术组早产儿胎龄及出生体重均大于手术组(PP1.3 及导管直径的平方/出生体重(d2/BW)比值>9 mm2/kg 的发生率均高于非手术组(PPP>0.05)。结论 对有临床症状且内科保守治疗或药物治疗无好转的早产儿PDA,外科结扎术是相对安全有效的方法。     

早产儿动脉导管开放的处理

动脉导管开放(PDA)是早产儿常见病症,导致早产儿血流动力学不稳定,严重者可危及生命,应积极处理.药物关闭PDA仍是最有效、方便和经济的治疗方法,吲哚美辛一直是内科保守治疗的主要用药,PDA关闭率为46%～89%,但吲哚美辛有效血药浓度安全范围较窄,且可导致肾功能障碍、颅内出血、坏死性小肠结肠炎和肠穿孔等不良反应.近年国外采用布洛芬治疗早产儿PDA,取得较好疗效,关闭率为73.0%～95.5%,且对肾脏、脑及消化道血流动力学影响显著减少.药物治疗无效且严重影响心肺功能者可选择手术治疗.     

Transcatheter closure of patent ductus arteriosus

Summary 1. A technique has been presented for transcatheter closure of a patent ductus arteriosus. 2. A 3.5-kg infant has been treated successfully in this manner. 3. The method should be considered in high-risk patients. 4. Further miniaturization of the system should make it suitable for use in premature infants critically ill as a result of ductal patency. 5. Increased experience will likely indicate that the technique is applicable to most patients who require ductus closure. This investigation was supported in part by Public Health Service Grant HL12307 from the National Heart, Lung and Blood Institute, and in part by Grants from The American Heart Association, Southeastern Pennsylvania and Delaware Chapters.     

低体重早产儿动脉导管未闭治疗进展

动脉导管未闭是一种新生儿常见疾病。在早产儿,尤其是低体重儿中其发病率更高。如未及时治疗,往往会导致新生儿颅内出血、呼吸窘迫综合征、慢性肺疾病等严重并发症。目前临床上有药物治疗、手术治疗、介入治疗及对症治疗,该文对低体重早产儿动脉导管未闭治疗的进展作一综述。     

极低与超低出生体重儿动脉导管未闭管理与支气管肺发育不良发生的关系

早产儿支气管肺发育不良( bronchopulmonary dysplasia,BPD)是早产儿特别是极低和超低出生体重儿常见的并发症之一。 BPD在其发生发展过程中受到多种因素的影响,其中动脉导管未闭( patent ductus arteriosus,PDA)及其临床管理,特别是PDA不同的治疗方案和治疗时机的选择对BPD发生的影响受到广泛关注。本文总结了早产儿PDA管理与BPD发生关系的研究进展,并在此基础上提出可能有利于降低早产儿BPD发生率的PDA管理建议。     

Unusual ultrasound finding of patent ductus arteriosus in a preterm infant

Summary Patency of the ductus arteriosus (PDA) is a common finding in small premature infants. Recently pulsed-Doppler-cross sectional echocardiography (PD-CSE) has been successfully used in these patients. We report a case of a premature infant with an unusual PD-CSE pattern.     

Retrolental fibroplasia in premature infants with patent ductus arteriosus treated with indomethacin

Sixteen premature infants were treated with indomethacin, either orally or intravenously, in order to close a symptomatic patent ductus arteriosus requiring mechanical ventilation. Positive effect was obtained in 4 of the 10 orally treated patients and in 1 of the 6 with intravenous administration. Immediate side effects were impairment of renal function, abdominal distension, and restlessness.Although the oxygen administration was guided using a transcutaneous oxymonitor, three severe cases of retrolental fibroplasia occurred. As indomethacin is a nonselective inhibitor of all prostaglandins, it might also cause a constriction of the retinal arteries, and as such be a factor in the development of retrolental fibroplasia in small premature infants.     

Clinical and echocardiographic diagnosis of patent ductus arteriosus in premature neonates

The ductus arteriosus frequently fails to close in premature neonates. Considerable difference in opinion exists around what signifies a hemodynamically significant patent ductus arteriosus (PDA) and how reliable clinical signs are in determining the degree of the left-to-right shunting. Although reliance on clinical signs alone could delay the diagnosis of a PDA, there is insufficient evidence to suggest that early treatment improves outcome. Echocardiography is often used as the gold standard for diagnosing a PDA. A combination of echocardiographic measurements may assist in the early diagnosis of a PDA with a hemodynamically significant degree of left-to-right shunting, especially in extremely premature babies, where closure can be significantly delayed. Decision to treat PDA should be based on a combination of clinical signs and echocardiographic parameters. Monitoring B-type natriuretic peptide may be useful in the diagnosing neonates with symptomatic PDA.     

应用Amplatzer堵闭器封堵0～1岁婴儿动脉导管未闭临床分析

目的　探讨应用AmplatzerDuctOccluder(ADO)封堵 0～ 1岁婴儿动脉导管未闭 (PDA)的可行性 ,并对其疗效及相关技术进行评价。方法　 30例PDA患儿 ,平均年龄 (7 4± 3 6 )个月 ,平均体重 (6 1± 2 7)kg ,15例合并肺动脉高压。所有患儿均应用ADO进行堵闭。结果　PDA最窄处直径平均 (4 8± 2 4 )mm (2 1～7 2mm) ,其中 2 0例 (6 6 7% )为大型PDA(>4 0mm)。 4例操作过程中输送鞘出现了扭曲弯折 (13 3% ) ,后换用Cook长鞘顺利完成堵闭 ,致使手术时间过长 (超过 12 0min)。 30例平均手术时间 (76 9± 30 1)min (4 5～15 0min) ,平均X线透视时间 (7 4± 5 2 )min(4～ 2 5min)。 30例平均随访 1 5年 ,仅 1例存在残余分流 ,完全闭合率达 96 7%。 2例出现降主动脉血流速度增快 (>2 0m/s) ,其余病例均未见溶血、堵闭器脱落、左右肺动脉及降主动脉狭窄。结论　应用ADO关闭 0～ 1岁婴儿PDA是安全、可行、有效的治疗方法 ,但对于体重 5 0kg的婴儿 ,装置及其输送系统尚需进一步改进。     

Prophylaxis of patent ductus arteriosus with ibuprofen in preterm infants

The aim of our study was to evaluate whether the prophylactic use of ibuprofen would reduce the incidence of significant patent ductus arteriosus (PDA) and to confirm the effectiveness of ibuprofen as rescue treatment in closing PDA. Eighty preterm infants with gestational age less than 34 wk with infant respiratory distress syndrome (iRDS) were randomized to receive intravenous ibuprofen lysine (10 mg/kg, followed by 5 mg/kg after 24 and 48 h) either within 24 h of life (group A) or after echocardiographic diagnosis of PDA (group B). To evaluate the severity of RDS in each patient, we calculated the initial and highest values of Oxygenation Index (O.I. = mean airway pressure x FiO2 x 100/PaO2) and Ventilatory Index (V.I. = O.I. x mechanical respiratory rate). Other studied variables were ventilatory support, renal function, biochemical and haematological profiles, frequency of bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). On the 3rd day of life, 8% (3/40) of patients of group A and 53% of patients (21/40) of group B (p < 0.0001) developed a significant PDA. Between patients of group B who presented PDA at 3 d of life 90% (19/21) had a closure of ductus arteriosus after ibuprofen treatment. Initial and highest values of O.I. and V.I. were similar in both groups A and B. No significant differences between the groups were observed in regard to respiratory support, renal function and frequency of BPD, IVH, NEC and ROP. Ibuprofen was not associated with adverse effects. Conclusion: Prophylactic treatment with ibuprofen reduces PDA occurrence in preterm infants with iRDS at 3 d of life in comparison with rescue treatment, but both modes are effective in closing the ductus without significant adverse effects.     

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目的探讨简易的超声心动图指标预测动脉导管开放(PDA)新生儿及婴儿日后动脉导管自行关闭的可能性及临床意义。方法对新生儿及婴儿期经彩色多普勒超声心动图证实的PDA患儿56例(其中早产儿8例,低出生体重儿18例)进行3、6、9和12个月随访观察,初诊年龄1-33(15.8±12.3)d。观察指标包括二维超声心动图测量的PDA最小直径(MD2DE),彩色多普勒血流显像测量的PDA分流束宽度(W JCDFI),并评估超声心动图指标对预测患儿1周岁时PDA自行关闭的价值。PDA关闭的判断标准为彩色多普勒血流显像无异常分流且频谱多普勒超声未能探及连续性分流频谱。结果随访过程中,随访3、6、9和12个月的PDA自行关闭率分别为23.2%、30.4%、32.1%和32.1%。若分别以首次测量的MD2DE≤3mm和≤2mm以及M JCDFI≤3mm和≤2mm为界限,则12个月随访结束时2种测量技术4项测量指标预测PDA关闭的敏感性为46.9%、80.0%、65.0%和83.3%(P<0.05),特异性为87.5%、94.4%、86.1%和81.9%(P<0.05),阳性预测值为83.3%、88.9%、72.2%和55.5%(P<0.05),阴性预测值为55.3%、89.5%、81.6%和81.8%(P<0.05),准确性为64.3%、89.3%、78.6%和82.1%(P<0.05)。结论简易超声心动图指标可较好地预测未闭动脉导管自行闭合的可能性,对患儿是否选择早期干预措施具有指导价值。     

Precordial contrast echocardiographic detection of patent ductus arteriosus in small preterm infants

Summary Clinical detection of patent ductus arterious (PDA) remains an important and challenging problem in the small preterm infant with respiratory distress. In this study, PDA was diagnosed in 28 small preterms using an improved contrast echocardiographic method. In these infants, the injection of saline into the aorta generated echoes which were imaged at the pulmonary valve. This was accomplished using a conventional M-mode ultrasound transducer applied at the usual precordial position. Contrast echo studies were compared with the degree of ductal patency shown by single film aortography. Ductal patency was detected by contrast echo in 29 of 31 instances of aortographically proven PDA. Indirect echo indices commonly used for detection of PDA (cardiac chamber enlargement) may be limited since factors other than left-to-right shunt can cause cardiac enlargement in distressed small preterms. This direct contrast echo technique is an easily performed, sensitive, qualitative method for confirmation of the diagnosis of PDA in small preterm infants. This work was supported in part by grant 5507 RR05551-17 from U.S. Public Health Service, Bethesda, Maryland Presented to members of the Cardiology Section at the 20th Annual Meeting of the Society for Pediatric Research, April 29–May 2, 1980, San Antonio, Texas     

Color Doppler flow mapping of the patent ductus arteriosus in very low birthweight neonates: Echocardiographic and clinical findings

Summary Forty-eight preterm infants (mean birthweight 1.0±0.3 kg; mean gestational age 28±3 weeks) underwent serial echocardiograms and physical examinations in order to determine the correlation between color Doppler flow mapping (CDFM) results and physical findings of a patent ductus arteriosus (PDA), the predictive value of early CDFM as an indicator of subsequent requirement for treatment of a PDA, and to determine the direction and duration of ductal shunting and the rate of ductal closure and opening. CDFM analysis and cardiac physical examination of left-to-right ductal shunting were usually concordant in infants with a large PDA shunt, the most reliable physical finding being increased precordial activity. CDFM studies on day 2 or 3 of postnatal life had prognostic value with regard to subsequent need for closing the PDA. Additional findings included the absence of right-to-left PDA shunting in infants <1 kg and <28 weeks gestation and the absence of ductal reopening in infants in whom it had closed spontaneously. After complete PDA closure using indomethacin, subsequent ductal reopening is uncommon, except in infants <25 weeks gestation and <700 g bodyweight.     

口服消炎痛和布洛芬治疗早产儿动脉导管未闭的比较

目的：静脉注射消炎痛是早产儿动脉导管未闭的常规治疗方法,但治疗过程中常出现一些副作用,如少尿、消化道出血、脑血流灌注减少。近年来,静脉注射布洛芬已用于治疗早产儿动脉导管未闭。布洛芬治疗不会减少脑血流灌注,也不会影响胃肠道和肾脏的血流动力学。伊朗目前尚无消炎痛和布洛芬的静脉制剂供应。该研究旨在比较这两种药的口服制剂治疗早产儿动脉导管未闭的疗效和安全性。方法：36例胎龄小于34周经超声心动图确诊患有动脉导管未闭的早产儿被随机分为两组,每组18人。一组给予消炎痛口服,每次0.2 mg/kg,24 h给药 1 次,共3次。另一组给予布洛芬口服,共 3 次,间隔时间为24 h,首剂为 10 mg/kg,随后两次各 5 mg/kg。用药后观察导管闭合率、副作用、并发症及临床过程。结果：用药后布洛芬组18例患儿动脉导管都闭合（100％）,而消炎痛组18例中有15例患儿动脉导管闭合（83.3%）（P＞0.05）。两组疗效差异统计学无显著性意义。治疗前后两组的血清尿素氮和肌酐含量差异也无显著性意义。消炎痛组发生了3例（16.6%）坏死性小肠结肠炎,布洛芬组则无,差异有显著性意义 (P＜0.05)。治疗1个月后两组成活率均为 94%（17／18）。消炎痛组1例死于坏死性小肠结肠炎,布洛芬组1例死于败血症。结论：口服布洛芬治疗早产儿动脉导管未闭和口服消炎痛治疗一样有效,而且坏死性小肠结肠炎的发生率较口服消炎痛治疗低。［中国当代儿科杂志,2007,9（5）：399-403］     

Echocardiographic systolic time intervals in premature infants with patent ductus arteriosus

Summary Thirty-six premature infants with respiratory distress syndrome and clinically significant patent ductus arteriosus (PDA) were studied by M-mode echocardiography before and after closure of the ductus. Before closure the ratio of left ventricular preejection period to left ventricular ejection time (LPEP/LVET) was .26±.03 (mean±SD). After closure of the ductus, LPEP/LVET was .38±.04 (mean±SD), significantly different from the value before closure but not significantly different from the value found in 21 control infants; also, a ratio < .30 was always associated with a clinically significant shunt. The combination of systolic time interval measurement with standard M-mode measurement of the left side of the heart enhanced echocardiographic detection of PDA in our series. Serial evaluation of systolic time interval measurements may provide a further index of left-to-right shunt through a PDA and be a valuable adjunct to the clinical management of these patients.Supported in part by grants from the Kentucky Heart Association.