Persistent Persistent Patent Ductus Arteriosus Research Articles

Narrative Review on Echocardiographic Evaluation of Patent Ductus Arteriosus in Preterm Infants.

Persistent Patent Ductus Arteriosus (PDA) is prevalent among extremely preterm infants, with its occurrence inversely related to gestational age. A persistent PDA correlates with increased mortality and morbidities such as intraventricular hemorrhage, pulmonary hemorrhage, chronic lung disease, bronchopulmonary dysplasia, and necrotizing enterocolitis as observed clinically. Conversely, numerous randomized controlled trials have failed to demonstrate significant benefits from PDA treatment. One contributing factor to these conflicting findings is that PDA affects each individual differently depending on the cardiovascular decompensation and its hemodynamic impact. PDA management should be based on the hemodynamic significance, rather than just the presence or size of PDA. This comprehensive narrative review paper describes echocardiographic parameters that allow a better understanding of the hemodynamic impact of PDA. A newer modality, like lung ultrasound, is also described here as an adjunct to assess the PDA impact on the lungs from pulmonary overcirculation.

Conservative Non-intervention Approach for Hemodynamically Significant Patent Ductus Arteriosus in Extremely Preterm Infants

While persistent patent ductus arteriosus (PDA) in preterm infants has been known to be associated with increased mortality and morbidities including bronchopulmonary dysplasia, and necrotizing enterocolitis, there is minimal evidence supporting their causal relationships, and most traditional medical and/or surgical treatments have failed to show improvements in these outcomes. As such, the pendulum has swung toward the conservative non-intervention approach for the management of persistent PDA during the last decade; however, the benefits and risks of this approach are unclear. In this mini review, we focused on whom, when, and how to apply the conservative non-intervention approach for persistent PDA, especially in extremely preterm infants.

Echocardiographic Diagnosis and Hemodynamic Evaluation of Patent Ductus Arteriosus in Extremely Low Gestational Age Newborn (ELGAN) Infants.

Persistent Patent ductus arteriosus (PDA) is a common finding in extremely low gestational age newborn infants and its prevalence is inversely proportional to the gestational age. The presence of a persistent PDA is associated with increased mortality and several significant morbidities including intraventricular hemorrhage, pulmonary hemorrhage, necrotizing enterocolitis, and chronic lung disease or bronchopulmonary dysplasia. However, treating PDA has not been demonstrated to have beneficial impact on the long term outcomes. Currently there is no consensus on whether to treat the PDA or not, and if treat, when to treat and how to treat. The echocardiography is the investigation of choice to diagnose PDA, estimating the magnitude of shunt volume and assessing its hemodynamic significance, and to exclude/diagnose any associated congenital heart defect before any intervention. Various echocardiographic parameters and staging/scoring systems have been described to help the clincians making the clinical decisions and some of theses scoring systems are quite complex to apply in a busy day to day clinical practice. This concised review paper is focused to help the clinicians in making a clinical decision based upon clincial and echocardiography parameters. Hence, only the parameters which are commonly used and helpful in making the clinical decisions in day to day clincial practice have been described in this paper.

PDA: Does it matter?

Management of persistent patent ductus arteriosus (PDA) continues to be a challenging issue. The attitude toward PDA has shifted in the opposite direction during the last 20 years, from advocating an aggressive and early closure toward a call for watchful observation. While persistent PDA may cause challenges in the medical management of preterm neonates secondary to volume overload, pulmonary edema or hemorrhage, hypotension, and impaired tissue perfusion, its contribution toward long-term neonatal morbidities including bronchopulmonary dysplasia (BPD), ROP, NEC, and NDI has not been substantiated. By advocating conservative management, it is clear now that the majority of the PDA cases show spontaneous closure and do not require treatment. However, there has not been agreement regarding what constitutes a hemodynamically significant PDA and when, if any, it should be targeted for treatment. With increasing concern regarding possible associated complications with PDA ligation, a new trend for transcatheter approach to PDA closure is expanding. In this review, we summarize current understanding of the pathophysiology, diagnosis, and management of PDA in preterm infants, and we make some recommendations regarding evidence-based approach.

Early haemodynamically significant patent ductus arteriosus does not predict future persistence in extremely preterm infants.

We assessed whether early haemodynamically significant patent ductus arteriosus (hsPDA) predicted persistent patent ductus arteriosus (PDA) in extremely preterm infants. This prospective observational study of 60 infants born at 22-27weeks of gestational age (GA) without any major congenital anomalies or heart defects was conducted at Uppsala University Children's Hospital from November 2012 to May 2015. Respiratory and systemic circulatory parameters were continuously recorded, and echocardiographic examinations performed daily during the first three days of life. Pharmacological treatment was initiated if hsPDA was found on days two to seven. Persistent PDA was diagnosed if hsPDA remained after pharmacological treatment or pharmacological treatment was contraindicated. The infants (56% male) had a median GA of 25+2weeks and 50% received pharmacological treatment. PDA was persistent in 30% and ultimately closed or insignificant in 70%. hsPDA on days two to seven was not associated with future persistent PDA (p=1.000). Mechanical ventilation (p=0.025), high mean airway pressure (p=0.020) and low ductal maximal flow velocity (Vmax ) (p=0.024) on day two were associated with future persistent PDA. Early hsPDA did not predict persistent PDA, but the early need for assisted ventilation and low ductal Vmax were associated with future persistent PDA in these extremely preterm infants.

RF58 PATENT DUCTUS ARTERIOSUS IN EARLY PRETERMS: SICILIAN AND CALABRIAN ON SITE EXPERIENCE

Introduction: The selection of extremely preterm infants with persistent patent ductus arteriosus (PDA) for surgical ligation after the failure of pharmacologic closure remains controversial in neonatology. No randomized clinical trial has examined the efficacy of surgery compared with conservative management among infants with persistent hemodynamically significant PDA after nonsteroidal anti-inflammatory drug treatment. Although surgical closure definitely closes a persistent PDA, promotes early extubation and decreases the mortality rate, it is also associated with short-term adverse events, including post-PDA ligation cardiac syndrome, vocal cord paralysis, chylothorax, and pneumothorax. We report our interregional experience based on a 24 h dedicated “onsite team” that performs surgical procedures in regional NICU. Methods: As a part of the agreement between the “Bambino Gesù” Pediatric Hospital in Rome and the Sicily Health Region Government the Centro Cardiologico Pediatrico del Mediterraneo, became the only center of reference for the diagnosis and treatment of congenital heart disease in Sicily. Due to the extent of the territory and the extreme fragility of the preterm infant, surgical ligation of the PDA was conducted by a dedicated team, consisting of a cardiac surgeon, anesthetist and two operating room nurses, directly at the bedside in NICU. From May 2011 to May 2018, 78 on-site procedures were performed. Median gestational age was 26 weeks (range 24–32), median weight at birth 800 grams (range 570–1380), median weight at surgery 1000 grams (range 540–1600) with 62.3% of patients weighing less than 900 grams. All infants were treated with ligation when indomethacin or pacetamol failed or was contraindicated. In our population 56% attempted closure with Pedea, 12% with paracetamol. In the remaining cases, the pharmacological treatment was contraindicated due to the presence of comorbidity (for example III-IV grade cerebral hemorrhage, renal or hepatic insufficiency). Results: 75% of treated patients have been discharged from the hospital and is still in follow up. No short-term adverse events were registered. Conclusion: in our experience we confirm that such an approach represent a valid and safe option for the baby and the whole medical team involved in medical and surgical procedure.

PC.43 Transcatheter closure of the patent ductus arteriosus in ex-premature infants in Scotland 2001–2010

AimsTo define characteristics and complications of ex-premature Scottish children having transcatheter closure of a persistent patent ductus arteriosus (PDA).MethodRetrospective analysis of cases from a national interventional paediatric cardiac centre at...

Failure of a repeat course of cyclooxygenase inhibitor to close a PDA is a risk factor for developing chronic lung disease in ELBW infants

BackgroundThe optimal treatment regimen or protocol for managing a persistent patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants has not been well established. This study was aimed at evaluating the failure rate of a cyclooxygenase (COX) inhibitor (COI) for PDA closure and to determine the incidence of a PDA requiring ligation in ELBW infants. We examined the clinical characteristics and risk factors that may predict the clinical consequences of failure of PDA closure by COI.MethodsMedical information on 138 infants with birth weight (BW) < 1000 gm who survived for > 48 hours was retrieved. Clinical characteristics and outcomes of patients whose PDAs closed with COI were compared with those who did not close.ResultsOf the 138 patients, 112 survived to discharge. Eighty (71.4%) of those who survived received 1-3 courses of COI treatment for a symptomatic PDA. A total of 32 (40%) failed COI treatment and underwent PDA ligation. Multivariable logistic regression analysis suggests that the observed differences in the outcomes in infants with or without symptomatic PDA can be explained by the babies with symptomatic PDA being more immature and sicker. No significant difference was seen in the incidence of chronic lung disease (CLD) in infants whose PDA was treated medically versus those who failed medical treatment and then underwent ligation. However, after adjusting for disease severity and other known risk factors, the odds ratio of developing CLD for surviving babies with a persistent PDA compared to those whose PDA was successfully closed with 1-2 courses of COI is 3.24 (1.07-9.81; p = 0.038).ConclusionsWhen successfully treated, PDA in ELBW infants did not contribute significantly to the adverse outcomes such as CLD, retinopathy of prematurity (ROP) and age at discharge. This suggests that it is beneficial for a hemodynamically significant PDA to be closed. The failure of a repeat course of COI to close a PDA is a major risk factor for developing CLD in ELBW infants.

Patent Ductus Arteriosus Ligation Alters Pulmonary Gene Expression in Preterm Baboons

Ibuprofen-induced ductus closure improves pulmonary mechanics and increases alveolar surface area in premature baboons compared with baboons with a persistent patent ductus arteriosus (PDA). Ibuprofen-treatment has no effect on the expression of genes that regulate pulmonary inflammation but does increase the expression of alpha-ENaC (the transepithelial sodium channel that is critical for alveolar water clearance). Although ligation eliminates the PDA, it does not improve pulmonary mechanics or increase alveolar surface area. We used preterm baboons (delivered at 67% of term gestation and ventilated for 14 d) to study whether the lack of beneficial effects, after PDA ligation, might be due to alterations in pulmonary gene expression. We found no differences in ventilation or oxygenation indices between animals that were ligated (n = 7) on day of life 6 and those that had a persistent PDA (n = 12) during the entire 14 d study. In contrast with no intervention, PDA ligation produced a significant increase in the expression of genes involved with pulmonary inflammation (COX-2, TNF-α, and CD14) and a significant decrease in alpha-ENaC sodium channel expression. We speculate that these changes may decrease the rate of alveolar fluid clearance and contribute to the lack of improvement in pulmonary mechanics after PDA ligation.

A Third Course of Indomethacin

The efficacy and the side effects of a third course of indomethacin in the treatment of persistent patent ductus arteriosus (PDA) were examined by Sangem et al. [6], and the results are presented in this issue of Pediatric Cardiology. In a retrospective analysis of 259 infants of gestational age \34 weeks with a PDA, one course of indomethacin resulted in closure in 76% of the patients. A second course of indomethacin in the remaining 61 infants with PDA caused closure in 42% of the patients. Of the remaining 38 patients with PDA, 11 were referred for surgical ligation of the PDA and 26 were treated with a third course of indomethacin. A total of 43% of the patients treated with a third course of indomethacin had closure of their PDA. Comparing patients treated with two courses of indomethacin to those treated with three courses, all measures of morbidity were similar except for an increased trend (p = 0.06) in periventricular leukomalacia (PVL) in patients treated with three courses. The authors of this study conclude that a prospective study comparing the effect of multiple courses to ligation in the treatment of persistent PDA should be performed.