Single-dose prophylactic ibuprofen therapy for patent ductus arteriosus in preterm infants

This study aimed to evaluate the short-term morbidities and efficacy of single-dose prophylactic intravenous ibuprofen for patent ductus arteriosus (PDA) on the first day of life in preterm infants.Data of 69 preterm infants with birth weight < 1250 g and gestational age < 30 weeks admitted to the neonatal intensive care unit were analyzed. Of these, 37 infants were assigned to the prophylactic treatment (PT) group and 32 were assigned to the nonprophylactic treatment (non-PT) group. Only the PT group administered intravenous ibuprofen (10 mg/kg) once within 6 hours after birth.Until postnatal day 7, ductal closure occurred in 11 (34.4%) infants in the non-PT group, and in 35 (94.6%) infants in the PT group, of which 30 (81.1%) infants had ductal closure on postnatal day 1. There were 2 (5.4%) infants in the PT group and 9 (28.1%) in the non-PT group who needed ibuprofen treatment due to moderate-to-large PDA after postnatal day 7. Preterm infants in the PT group were less likely to develop an intraventricular hemorrhage (≥grade 2) (adjusted odds ratio 0.007, 95% confidence interval 0.01–0.45), had a shorter duration of invasive ventilatory support and central venous catheter, and earlier postnatal age to achieve feeding of 50 and 100 mL/kg/day compared with those in the non-PT group.Single-dose prophylactic intravenous ibuprofen on the first day of life decreased the occurrence of a persistent PDA and intraventricular hemorrhage (≥grade 2), and reduced the duration of invasive ventilatory support, central venous catheter use, and hospital stay.     

Fechamento Percutâneo do Canal Arterial em Pacientes Prematuros Abaixo de 2 Kg: Experiência Inicial Brasileira

BackgroundThe presence of patent ductus arteriosus can be as high as 50% in preterm babies. Hemodynamically significant patent ductus arteriosus is a common cause of delayed weaning of respiratory support and an important risk factor of necrotizing enterocolitis, intraventricular hemorrhage, and bronchopulmonary dysplasia in this population.ObjectiveThe aim of this study is to describe an initial experience of percutaneous closure of the ductus arteriosus in preterm infants weighing less than 2 kg.MethodsThis was a prospective study, comprised of 14 consecutive patients submitted to percutaneous closure of ductus arteriosus between March 2020 and February 2021 in 6 institutions in Brazil.ResultsMean gestational age was 28.45±3.14 weeks, mean age at the procedure was 38.85±17.35 days and mean weight was 1.41 ±0.41 kg; 79% of the patients were under mechanical ventilation, and 79% had been submitted, on average, to a 1.5 cycle of non-steroidal anti-inflammatory drugs. Most patients were weaned off of mechanical ventilation in a mean of 12.6 ±7.24 days after the procedure. Success rate was 100%. No procedure-related mortality was observed.ConclusionThis study concluded that percutaneous closure of ductus arteriosus in premature babies below 2 kg has satisfactory results and a low complication rate in this study sample.     

Outcomes of Early Ligation of Patent Ductus Arteriosus in Preterms,Multicenter Experience

Persistent ductal patency may have serious effects in preterm infants. Analysis of the results of different trials were inconclusive in determining whether medical or surgical closure of the ductus is preferable and what is the best timing for surgical intervention.The aim of this study was to evaluate the effect of timing of surgical closure of patent ductus arteriosus (PDA) on ventilatory, hemodynamic, and nutritional status of preterm infants.The authors retrospectively looked at the outcomes of surgical ligation of PDA from January 2010 to June 2014 at 2 Saudi neonatal intensive units at 2 tertiary care centers and the authors compared the results of early ligation (before 3 weeks) to the late ligation (after 3 weeks) regarding different hemodynamic, ventilatory, and nutritional parameters.A total of 120 preemies were included (75 preemies with early ligation and 45 with late ligation of PDA). The early ligation group had shorter duration of assisted ventilation of 10 (8–37) days as compared with 37 (26–90) days in the late ligation group (P < 0.05). The median fraction of inspired oxygen, needed to maintain good oxygen saturation in patients, was higher in the late ligation group [0.29 (0.21–0.70)] than in the early group [0.23 (0.21–0.55)] at 24 hours postoperatively. Full oral feeding was achieved earlier in the early ligation group than in the late group, 29 (15–73) days of life versus 53 (34–118) days of life, respectively (P < 0.05). Body weight at 36 weeks postconceptional age was higher in the early group—2100 (1350–2800) g—than in the late group—1790 (1270–2300) g—(P < 0.05).Our study demonstrated that earlier surgical ligation of the PDA in preterm infants has a more favorable nutritional and ventilatory outcome.     

Management of patent ductus arteriosus in preterm infants.

OBJECTIVE: To evaluate the incidence of symptomatic patent ductus arteriosus (PDA) in preterm infants, and the results of the intravenous indomethacine treatment and surgery. METHODS: Among 394 preterm infants (<37 weeks), symptomatic PDA was diagnosed by echocardiography in 51 babies and they were examined retrospectively. All infants were managed conservatively and then IV indomethacine was given to non-responders (n=30). Surgical closure was performed in 12 babies. RESULTS: The incidence of symptomatic PDA in preterm infants was 12.9%: median age: 3 days, mean birth weight: 1434+/-540 g (540-2900g) and mean gestational age (GA) 30.9+/-3.3 weeks (23-37 weeks). With indomethacine, ductal closure was achieved in 70% infants. Early clinical improvement was observed in all cases that underwent surgery and most of them had a low birth weight (<1500 g) and an early gestational age (<32 weeks). None of them died due to operation. CONCLUSION: The incidence of symptomatic PDA is high in preterm infants. Treatment with indomethacine improves ductal closure and is associated with few reversible adverse effects. In the other hand, early clinical improvement and high success rate were achieved after surgery. If indomethacine fails to achieve ductal closure, decision of surgery must be made immediately.     

Surgical Closure of Patent Ductus Arteriosus in Preterm Low Birth Weight Infants

Background and Aim of the Study. In many preterm low‐birth‐weight infants, ductus arteriosus fails to close spontaneously. This study evaluates the results of surgical ligation of symptomatic patent ductus arteriosus (PDA) in preterm low birth weight infants. Methods. We reviewed the medical records of all infants undergoing surgical closure of PDA from January 1987 to December 2005. Demographic data, age and weight at operation, surgical technique to close PDA and outcome were analyzed. Results. One hundred and forty‐five infants underwent surgical closure of PDA in which either indomethacin treatment had failed or was contraindicated. The mean gestational age was 25.5 ± 2.3 (range 24–36 weeks) and the mean birth weight was 837.7 ± 277.2 g (450–1000 g). The average age and weight at operation were 14.1 (±1.8) days and 881.7 g (±338.1), respectively. PDA was surgically closed by left thoracotomy using either nonabsorbable suture (73%) or hemoclips (27%). Postoperative complications occurred in 10 patients, which included intraoperative bleeding (6), pneumothorax (1), left vocal cord paralysis (1), lymphatic leak (1), and injury to left phrenic nerve (1). There was no mortality related to surgical closure of PDA. Conclusion. We conclude that surgical closure of hemodynamically significant PDA is safe and effective in preterm low birth weight infants when pharmacological treatment is ineffective or contraindicated. The associated morbidity is minimal and no surgery‐related mortality was observed.     

经导管堵塞婴幼儿动脉导管未闭89例体会

目的探讨经导管堵塞婴儿动脉导管未闭的疗效。方法对８９例动脉导管未闭患儿采用了４种不同堵塞装置治疗。结果总成功率９８．８８％（８８／８９），失败１例，严重并发症２例，术后２４小时内残余分流１９例（２１．３％），经１个月～３．５年随访，微量残余分流７流（７．０８％）。结论经心导管堵婴幼儿动脉导未闭安全、有效、操作简单、适应证广，可作为治疗婴幼儿动脉导管未闭的首选方法。     

Qual Deve Ser o Tratamento de Primeira Linha para o Fechamento de Persistência de Canal Arterial Hemodinamicamente Significativo em Bebês Prematuros?

BackgroundIt is important which medicine to use as a first-line treatment to close the duct.ObjectivesThe aim of this study is to compare the effectiveness and side effects of intravenous (IV) forms of ibuprofen and paracetamol and to contribute to the literature investigating the first drug selected in the medical treatment of patent ductus arteriosus (PDA).MethodsOur study was conducted between January 2017 and December 2019. Premature infants with birth weight (BW) ≤1500 g and gestational age (GA) ≤32 weeks were included in the study. In the study period, all infants with hemodynamically significant patent ductus arteriosus (hsPDA) were given rescue intravenous (IV) ibuprofen as a primary medical treatment or IV paracetamol treatment if there were contraindications for ibuprofen. The patients were divided into two groups: patients receiving IV ibuprofen and patients receiving IV paracetamol.ResultsOf these patients, 101 were given IV paracetamol and 169 were given IV ibuprofen. The success rate of PDA closure with first-course treatment was 74.3% in the IV paracetamol group and 72.8% in the IV ibuprofen group (p=0.212).ConclusionsOur results show that IV paracetamol is as effective as IV ibuprofen in the first-line treatment of hsPDA, and can become the preferred treatment for the management of hsPDA.     

Transcatheter device closure of patent ductus arteriosus without arterial access – Single institution experience

ObjectiveRetrospective analysis of feasibility, safety and advantages of device closure of patent ductus arteriosus (PDA) using only venous access.BackgroundArterial access for transcatheter device closure of PDA has been a standard practice, but has inherent complications, especially in infants.MethodRecords of patients who underwent PDA device closure from 2004 to 2012 were reviewed. Echocardiography was used for patient selection and for assessment of procedural outcome.Result151 out of 179 patients underwent PDA device closure with venous access alone, weighing 2.2–58 kg with half <10 kg and follow up of 6 months–8 years. Fluoroscopic time ranged from 2.2 to 16 min. Immediate closure was achieved in 146 patients. Two patients had new-onset left pulmonary artery turbulence and one had residual flow.ConclusionPDA device closure without arterial access can be accomplished safely and effectively in vast majority of patients including infants.     

Transcatheter closure of a patent ductus arteriosus in a preterm infant with an Amplatzer Vascular Plug IV device

Rapid advances in paediatric interventional cardiology allow transcatheter closure of patent ductus arteriosus (PDA) in increasingly smaller patients. We describe a successful transcatheter closure of a large tubular PDA in a symptomatic preterm infant of 2,210 g using an Amplatzer Vascular Plug IV device. © 2010 Wiley‐Liss, Inc.     

极低体重早产儿动脉导管未闭的治疗

目的:探讨极低体重早产儿动脉导管未闭(PDA)的治疗方法。方法:本研究回顾性分析6例经外科手术治疗的PDA的极低体重早产儿的临床特点。结果:4例患者布洛芬治疗失败、2例患者因药物禁忌行动脉导管结扎术,术后由对呼吸机依赖转为3～4d过渡脱机,胃肠内喂养耐受性及体重增加显著改善[(45±41)∶(258±77)g/周,P<0.001],5例存活患者均无手术并发症,1例患者死于早产儿并发症。结论:对于有手术指征的PDA的极低体重早产儿,外科手术结扎是安全而有效的方法。     

Usefulness of pulsed doppler echocardiography in the diagnosis and medical therapy of patent ductus arteriosus in the newborn with respiratory distress

In preterm infants patent ductus arteriosus (PDA) may worsen the clinical course of Respiratory Distress Syndrome (RDS). Indomethacin is usually effective in producing duct closure in the first days of life, but clinical diagnosis is often difficult to perform in these patients. In recent years Pulsed Doppler Cross-Sectional Echocardiography (PD-CSE) has made it possible to identify the duct and to assess noninvasively the characteristics of blood flow within it. The aim of this study was to verify the utility of PD-CSE in the early diagnosis of PDA and to provide the basis for a more effective drug therapy. Among 51 patients with RDS, a significant PDA was evidenced in 20 with PD-CSE and in only 8/20 with physical and E-TM examination (p less than 0.01). Indomethacin administration produced duct closure in 19/20 patients (95%). In this study PD-CSE has been more sensitive than the other noninvasive procedures in the diagnosis of PDA; moreover, the success with drug therapy demonstrates the utility of this procedure in providing the basis of a more effective treatment of the duct.     

Echocardiographic guidance for transcatheter patent ductus arteriosus closure in extremely low birth weight infants

Echocardiographic imaging provides real‐time guidance during transcatheter patent ductus arteriosus (PDA) closure in extremely low birth weight (ELBW) infants. Transthoracic echocardiogram provides detailed assessment of the PDA and surrounding structures prior to, during, and after transcatheter closure. This article aims to review the different echocardiographic techniques and concepts utilized during transcatheter PDA closure in ELBW infants.     

Non-surgical closure of patent ductus arteriosus in children with the Rashkind double disk occluder

Since the first clinical application of transcatheter closure technique for patent ductus arteriosus in children and infants in 1977 by Rashkind and Coll., this technique is routinely performed only in a few major Pediatric Cardiology Centers. We report our successful series which is the first of its kind both in Italy and in Southern Europe. The series included 11 children aged 1.6 to 10 years (mean age 4.5 years) all affected with patent ductus arteriosus (PDA). Subaortic stenosis (1) and ventricular septal defect with pulmonary stenosis (1) were associated anomalies. In all of the cases, after the standard percutaneous cardiac catheterization, the Mullins method was attempted to advance and deliver the Rashkind PDA double-disk occluder. Successful closure was accomplished in 10 while almost complete closure was achieved in the 11th. Normal Doppler flow pattern after the procedure confirmed the successful results. No complications occurred. Although our experience is limited, non-surgical PDA closure provided an excellent alternative to surgical procedure.     

Effect of patent ductus arteriosus on the heart in preterm infants

There continues to be controversy on the long‐term effects of a patent ductus arteriosus (PDA) and its management. However, the hemodynamic effects of a large PDA in a preterm infant are well known. This article aims to provide insight into the adaptive changes and remodeling effects of a PDA on the myocardium in preterm infants.     

The timing of spontaneous closure of the ductus arteriosus in infants with respiratory distress syndrome

Previous studies evaluating the incidence of patent ductus arteriosus have not made a distinction between physiologic ductal patency and abnormally persistent ductus arteriosus. However, it has recently been shown that healthy premature infants without respiratory distress syndrome (RDS) undergo spontaneous closure of the ductus arteriosus in the first 4 days of life at times comparable to full-term infants. Thus, ductal patency within this time frame would appear to be physiologic. Although sick premature infants are well recognized to be at risk for ductal shunting, the purpose of this investigation was to evaluate systematically the actual impact that RDS has on duration of ductal shunting by assessing the timing of spontaneous functional closure. The presence of ductal shunting was evaluated using echocardiographic color flow Doppler techniques. Thirty-six premature infants (30 to 37 weeks gestational age) were evaluated. By the fourth day of life, only 4 of 36 (11.1%) of the infants continued to have evidence of ductal patency. The remainder of the infants underwent spontaneous functional closure of the ductus arteriosus at times comparable to healthy infants without RDS. For most infants greater than or equal to 30 weeks gestation, uncomplicated RDS does not alter the usual timing of functional ductal closure.     

Assessment of the ductus arteriosus in preterm infants utilizing suprasternal two-dimensional/Doppler echocardiography

Evaluation for patent ductus arteriosus by both Doppler examination and direct two-dimensional echocardiographic visualization has been reported in infants and children. However, visualization of a patent ductus arteriosus in preterm infants with lung disease has been difficult. Using a recently developed 7.5 MHz mechanical scanner with interfaced two-dimensional directed pulsed Doppler ultrasonography, 36 examinations were performed from a suprasternal approach in 27 patients (age range 1 day to 3 months, mean 18 days; weight range 490 to 2,500 g, mean 1,260). Complete imaging for evaluation of patency of the ductus arteriosus was successful in 33 (92%) of 36 examinations, and imaging of the pulmonary end of the ductus arteriosus was successful in all. In 18 examinations, the ductus arteriosus was closed by both two-dimensional echocardiography and Doppler examination. In four cases the ductus arteriosus was widely patent by both two-dimensional echocardiography and Doppler examination. Eleven echocardiographic examinations revealed a narrowed ductus arteriosus, and of these, 10 (91%) showed Doppler findings of patent ductus arteriosus. It is concluded that combined two-dimensional/Doppler echocardiographic assessment allows confident detection of both a large unrestrictive and a small, stenotic patent ductus arteriosus in preterm infants with lung disease.     

Patent ductus arteriosus in preterm newborns: A tertiary hospital experience

IntroductionPatent ductus arteriosus (PDA) in preterm infants has been associated with increased mortality and comorbidities. This study aimed to characterize the population of preterm infants diagnosed with PDA and to identify predictive factors of response to medical treatment of PDA.MethodsAn eight-year retrospective observational study was carried out, which included all preterm infants with a gestational age (GA) between 23 and 32 weeks diagnosed with PDA, admitted to the Neonatal Unit of the CHUSJ. Univariate comparative analysis was performed, and models for predicting the effectiveness of PDA treatment with ibuprofen were explored by multivariate logistic regression analysis.Results115 cases were included and 34 were excluded, with a final sample of 81 preterm infants with PDA. The univariate analysis revealed significant differences in the closure efficacy via medical treatment with ibuprofen in several variables, and a multivariate logistic regression model was obtained (discriminative capacity 72.2%, sensitivity 98.1%, specificity 57.1%), taking into account the effect of GA, type of delivery, need for diuretics treatment and platelet transfusion.ConclusionThis study enabled the population of preterm infants diagnosed with PDA to be characterized and the identification of a predictive model that can help predict the efficacy of medical treatment and thus contribute to optimizing the medical approach to the non-responders.     

Effect of patent ductus arteriosus on pulmonary vascular disease

The hemodynamic effects of a patent ductus arteriosus (PDA) are well known including systemic hypoperfusion and volume overload on the left ventricle. This article aims to provide a review of the long‐standing effect of a hemodynamically significant PDA on the pulmonary vasculature and the role of cardiac catheterization in preterm infants with a PDA and pulmonary hypertension.     

Effect of oral ibuprofen on patent ductus arteriosus in premature newborns

Background aim of the studyPatent ductus arteriosus (PDA), a common finding among premature infants, is conventionally treated by intravenous indomethacin. Intravenous ibuprofen was recently shown to be as effective and to have fewer adverse reactions in preterm infants. If equally effective, then oral ibuprofen for PDA closure would have several important advantages over the intravenous route. This study was designed to determine whether oral ibuprofen treatment is efficacious and safe in closure of a PDA in premature infants.Patients and methodsThirty-three premature group I (study group) were treated with ibuprofen 10 mg/kg administered through a feeding tube. Thirty-three premature group II (control group) receive placebo the two imaging procedures were again performed 24 h after each ibuprofen dose. When the PDA was still hemodynamically significant, as demonstrated by echocardiography, and there was no evidence of deterioration in brain ultrasonography, a second dose of ibuprofen 5 mg/kg (placebo for control) was administered. A third equivalent dose was given after another 24 h if necessary. Cranial ultrasound was repeated 1 week after the last ibuprofen dose and again before discharge from the ward. Hematochemical analysis was preformed daily in the unit during the first days of life.ResultsIn the study group the rate of PDA closure was 93.9% (31 of 33 cases) while in the control group the rate of PDA closure was 30.3% (10 of 33 cases) with significant difference in between. There was no reopening of the ductus after closure had been achieved. No infant required surgical ligation of the ductus in study group while in the control group 24.2% (8 of 33 cases) were required surgical ligation (Table 2). Twenty-one newborns were treated with 1 dose of ibuprofen, 9 were treated with 2 doses, and the remaining 3 were treated with 3 doses.ConclusionOral ibuprofen is an effective and safe alternative to intravenous ibuprofen for PDA closure in premature infants.     

Increased constriction of the ductus arteriosus by dexamethasone, indomethacin, and rofecoxib in fetal rats.

BACKGROUND: To find a better treatment for patent ductus arteriosus (PDA) in premature infants, the present study investigated the synergism of clinical doses of dexamethasone, indomethacin, and rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on the fetal ductus arteriosus (DA) in rats. METHODS AND RESULTS: Dexamethasone (0.3 mg/kg), indomethacin (0.3 mg/kg), and rofecoxib (0.3 mg/kg), alone or in combination, were administered to preterm (d19) and near-term (d21) fetal rats. The ratio of the inner diameter of the DA to that of the main pulmonary artery (PA) (DA/PA) was studied at 2, 4 and 8 h after drug administration, using a rapid whole-body freezing method. In near-term rats, the combined administration of dexamethasone and indomethacin caused severe constriction, with a DA/PA ratio of 0.52+/-0.08 at 8 h, whereas the DA/PA ratios were 0.83+/-0.03 and 0.90+/-0.02 with dexamethasone and indomethacin, respectively. Combined administration of dexamethasone and rofecoxib also caused severe constriction, with a DA/PA ratio of 0.64+/-0.07 at 8 h, compared with the DA/PA ratio of 0.92+/-0.03 with rofecoxib alone. CONCLUSIONS: Combined therapy may be an option in the medical management of PDA in premature infants before considering surgical treatment.